1,616 results match your criteria European Journal of Medical Genetics [Journal]


Unusual clinical description of adult with Timothy syndrome, carrier of a new heterozygote mutation of CACNA1C.

Eur J Med Genet 2019 Apr 15. Epub 2019 Apr 15.

Service Génétique, Génétique Clinique, CHU, Caen, France; Normandy University, UNICAEN, BIOTARGEN, Caen, France.

CANAC1C encodes for the main cardiac L-type calcium channel and mutations on it lead to a prolonged QT interval in Timothy Syndrome (TS). We provide a new de novo constitutional heterozygote missense variation in CACNA1C in a living adult woman, also carrier of the known c.2146-1G>C heterozygous variation of PKP2 inherited from her father. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183083
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http://dx.doi.org/10.1016/j.ejmg.2019.04.005DOI Listing
April 2019
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Abnormal cleavage and developmental arrest of human preimplantation embryos in vitro.

Eur J Med Genet 2019 Apr 14. Epub 2019 Apr 14.

The Evewell, 61 Harley Street, London, W1G 8QU, UK; School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK. Electronic address:

Despite improvements in culture conditions and laboratory techniques still only about 50% of human embryos reach the blastocyst stage of development in vitro. While many factors influence embryo development, aberrant cleavage divisions have only recently been shown to directly affect the genome in individual cells of human embryos resulting in chromosome loss, mosaicism and cell arrest. In this article we review the current literature in the area of aberrant cleavage in human embryos and its effect on blastocyst development. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.04.008DOI Listing

Next generation sequencing in recurrent pregnancy loss-approaches and outcomes.

Eur J Med Genet 2019 Apr 13. Epub 2019 Apr 13.

Department of Pathology and Laboratory Medicine, University of British Columbia and, Child and Family Research Institute, 950 West 28th, Vancouver BC, Canada. Electronic address:

Next generation sequencing (NGS) has revolutionized the diagnosis of postnatal genetic diseases, but so far has been used less frequently to study reproductive disorders. Here we provide an overview of approaches and outcomes of genome sequencing for identifying causes of recurrent pregnancy loss (RPL). This includes exome sequencing to look for pathogenic sequence changes in the whole exome or in a preselected list of genes considered important for early embryonic development and pregnancy maintenance, as well as low coverage whole genome sequencing useful for identifying cryptic balanced chromosome rearrangements and copy number variants (CNVs) in couples with RPL and miscarriages. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.04.001DOI Listing

Genetic Counselling to Genomic Counselling: an evolution not revolution.

Eur J Med Genet 2019 Apr 13. Epub 2019 Apr 13.

Wellcome Genome Campus, Society and Ethics Research Group, Connecting Science, Hinxton, Cambridge; Faculty of Education, University of Cambridge, Cambridge; Chair of the Association of Genetic Nurses and Counsellors (2018/2019), UK and Republic of Ireland. Electronic address:

Genome sequencing as a technology is rapidly transitioning from research into healthcare. By 2025 over 60 million patients across the globe will have their genomes sequenced in a healthcare setting [1]. 'Genomic medicine', could also now just be called 'Medicine' with the added benefit of genomic technology available as part of the patient testing repertoire. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.04.010DOI Listing

Further delineation of CDC45-related Meier-Gorlin syndrome with craniosynostosis and review of literature.

Eur J Med Genet 2019 Apr 12. Epub 2019 Apr 12.

Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Division of Nursing, KK Women's and Children's Hospital, Singapore. Electronic address:

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CDC45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.04.009DOI Listing
April 2019
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Novel EXOSC3 pathogenic variant results in a mild course of neurologic disease with cerebellum involvement.

Eur J Med Genet 2019 Apr 12. Epub 2019 Apr 12.

Heinrich-Heine-University, Medical Faculty, Institute of Human Genetics, Düsseldorf, Germany; Heinrich-Heine-University, Medical Faculty, Center of Rare Disorders, Düsseldorf, Germany. Electronic address:

EXOSC3-related autosomal recessive neurodevelopmental disorders are rare entities with variable clinical course and prognosis. They are characterized by hypoplasia of cerebellar structures and pons, degeneration of the anterior horn cells and motor as well as neurocognitive impairment. Phenotypic expression is variable with an overall poor outcome. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.04.006DOI Listing

Phenotypic presentations of Hajdu-Cheney syndrome according to age - 5 distinct clinical presentations.

Eur J Med Genet 2019 Apr 10. Epub 2019 Apr 10.

Department of Clinical Genetics, Aarhus University Hospital, Denmark; Pediatrics and Adolescent Medicine, Centre for Rare Diseases, Aarhus University Hospital, Denmark.

We present five Danish individuals with Hajdu-Cheney syndrome (HJCYS) (OMIM #102500), a rare multisystem skeletal disorder with distinctive facies, generalised osteoporosis and progressive focal bone destruction. In four cases positive genetic screening of exon 34 of NOTCH2 supported the clinical diagnosis; in one of these cases, mosaicism was demonstrated, which, to our knowledge, has not previously been reported. In one case no genetic testing was performed since the phenotype was definite, and the diagnosis in the mother was genetically confirmed. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183082
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http://dx.doi.org/10.1016/j.ejmg.2019.04.007DOI Listing
April 2019
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An extremely severe case of Aicardi-Goutières syndrome 7 with a novel variant in IFIH1.

Eur J Med Genet 2019 Apr 6. Epub 2019 Apr 6.

Division of Neonatology, Center for Maternal-Fetal, Neonatal, and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan.

We describe herein an extremely severe case of Aicardi-Goutières syndrome 7 (AGS7). The female patient was the daughter of nonconsanguineous parents and developed cardiomegaly, pericardial effusion, splenomegaly, and intracranial calcification during the fetal period. Because her cardiotocogram showed a non-reassuring fetal status, she was delivered at 29 weeks and 4 days of gestation by an emergency cesarean section. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.04.003DOI Listing
April 2019
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Heart transplantation in Danon disease: Long term single centre experience and review of the literature.

Eur J Med Genet 2019 Apr 5. Epub 2019 Apr 5.

Department of Cardiothoracic Science, Azienda Sanitaria Universitaria Integrata and IRCAB Foundation, Udine, Italy.

Danon disease is characterized by hypertrophic cardiomyopathy, skeletal myopathy, and intellectual disability due to deficiency of the lysosome-associated membrane protein-2 (LAMP-2). Although heart transplantation is considered an option for end stage Danon cardiomyopathy, scarce information is available about long term follow up. We report on long term follow up (14. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.04.002DOI Listing
April 2019
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Time lapse: A glimpse into prehistoric genomics.

Eur J Med Genet 2019 Mar 25. Epub 2019 Mar 25.

School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK. Electronic address:

For the purpose of this review, 'time-lapse' refers to the reconstruction of ancestral (in this case dinosaur) karyotypes using genome assemblies of extant species. Such reconstructions are only usually possible when genomes are assembled to 'chromosome level' i.e. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.03.004DOI Listing

Identification of a novel PCNT founder pathogenic variant in the Israeli Druze population.

Eur J Med Genet 2019 Mar 25. Epub 2019 Mar 25.

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Majewski Osteodysplastic Primordial Dwarfism type II (MOPDII) is a form of dwarfism associated with severe microcephaly, characteristic skeletal findings, distinct dysmorphic features and increased risk for cerebral infarctions. The condition is caused by bi-allelic loss-of-function variants in the gene PCNT. Here we describe the identification of a novel founder pathogenic variant c. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.03.007DOI Listing

Experts reflecting on the duty to recontact patients and research participants; why professionals should take the lead in developing guidelines.

Eur J Med Genet 2019 Mar 20. Epub 2019 Mar 20.

Amsterdam UMC, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands.

Sequencing technology is increasing the scale of information that could benefit patients who have been tested in the past. This raises the question whether professionals have a duty to recontact such patients or their families. There is currently no clear basis for a legal duty to recontact, and professional guidelines are limited. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.03.006DOI Listing

Nasal fistula, epidermal cyst and hypernatremia in a girl presenting holoprosencephaly due to a rare ZIC2 point mutation.

Eur J Med Genet 2019 Mar 17. Epub 2019 Mar 17.

Clinical Genetics, UFCSPA and Santa Casa de Misericórdia de Porto Alegre (SCMPA), RS, Brazil; Graduate Program in Pathology, UFCSPA, RS, Brazil. Electronic address:

Holoprosencephaly is the most common brain malformation in humans and it is a complex genetic disorder. We report on a patient with holoprosencephaly caused by a rare ZIC2 mutation presenting a bifid nose associated with a nasal fistula and an epidermal cyst, besides hypernatremia. The patient was a 1 year and 4 months old girl that developed an important neuropsychomotor delay. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.03.005DOI Listing
March 2019
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Telomeres and genomic instability during early development.

Authors:
David L Keefe

Eur J Med Genet 2019 Mar 9. Epub 2019 Mar 9.

Department of Ob/Gyn, NYU Langone Medical Center, 550 First Avenue, NBV 9N1A, New York, 10012, New York, USA. Electronic address:

Genomic instability is widespread during early embryo development. Aneuploidy, mosaicism, and copy number variants (CNVs) commonly appear in human preimplantation embryos. Both age-dependent meiotic aneuploidy and age-independent mitotic aneuploidy and CNVs occur In human embryos. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.03.002DOI Listing

Extending the phenotype of Xia-Gibbs syndrome in a two-year-old patient with craniosynostosis with a novel de novo AHDC1 missense mutation.

Authors:
Evren Gumus

Eur J Med Genet 2019 Mar 8. Epub 2019 Mar 8.

Department of Medical Genetics, Faculty of Medicine, University of Harran, Sanliurfa, 63000, Turkey. Electronic address:

Xia-Gibbs syndrome (Mental retardation, autosomal dominant 25; MRD25) [MIM 615829] is a rare autosomal dominant disease characterized by mental retardation, developmental delay, speech delay, structural brain anomalies, hypotonicity, protuberant eyes, visual problems, laryngomalacia and snoring. Since the first description in 2014, fewer than 50 patients with Xia-Gibbs syndrome have been noticed in the literature. We describe here 2 years 2 months old girl with developmental delay, brain anomalies, laryngomalacia and craniosynostosis. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.03.001DOI Listing
March 2019
2 Reads

Ten new cases of Balanced Reciprocal Translocation Mosaicism (BRTM): Reproductive implications, frequency and mechanism.

Eur J Med Genet 2019 Mar 8. Epub 2019 Mar 8.

Istituto Auxologico Italiano, IRCCS, Lab. di Citogenetica Medica, Milano, Italy.

Chromosomal anomalies are well known to be an important cause of infertility, sterility and pregnancy loss. Balanced Reciprocal Translocation Mosaicism (BRTM) is an extremely rare phenomenon, mainly observed in subjects with a normal phenotype accompanied by reproductive failure. To date the mechanism of origin and the incidence of BRTM are poorly defined. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.03.003DOI Listing

CNTN6 copy number variations: Uncertain clinical significance in individuals with neurodevelopmental disorders.

Eur J Med Genet 2019 Mar 2. Epub 2019 Mar 2.

Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, 43205, USA; The Ohio State University College of Medicine, Columbus, OH, 43210, USA. Electronic address:

Copy number variations (CNVs) of the CNTN6 gene - a member of the contactin gene superfamily - have been previously proposed to have an association with neurodevelopmental and autism spectrum disorders. However, no functional evidence has been provided to date and phenotypically normal and mildly affected carriers complicate the interpretation of this aberration. In view of conflicting reports on the pathogenicity of CNVs involving CNTN6 and association with different phenotypes, we, independently, evaluated clinical features of nineteen patients with detected CNV of CNTN6 as part of their clinical microarray analysis at Children's Mercy and Nationwide Children's Hospitals for the period of 2008-2015. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.02.008DOI Listing
March 2019
2 Reads

Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome.

Eur J Med Genet 2019 Feb 21. Epub 2019 Feb 21.

Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India; Department of Laboratory Medicine and Pathology, Rochester, MN, 55905, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address:

Say-Meyer syndrome is a rare and clinically heterogeneous syndrome characterized by trigonocephaly, short stature, developmental delay and hypotelorism. Nine patients with this syndrome have been reported thus far although no causative gene has yet been identified. Here, we report two siblings with clinical phenotypes of Say-Meyer syndrome with moderate to severe intellectual disability and autism spectrum disorder. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183047
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http://dx.doi.org/10.1016/j.ejmg.2019.02.007DOI Listing
February 2019
9 Reads

Diagnosis and clinical delineation of mosaic tetrasomy 5p.

Eur J Med Genet 2019 Feb 21. Epub 2019 Feb 21.

833 Chestnut Street, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, U19107, USA. Electronic address:

Objective: Our objective was to review the phenotypic and genetic characteristics of tetrasomy 5p from the fetal period until adulthood including prenatal diagnostic evaluations.

Background: Tetrasomy 5p is a rare chromosomal abnormality. Of the 14 reports, most document mosaic tetrasomy 5p resulting from a supernumerary marker chromosome or isochromosome. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.02.006DOI Listing
February 2019
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Tissue variations of mosaic genome-wide paternal uniparental disomy and phenotype of multi-syndromal congenital hyperinsulinism.

Eur J Med Genet 2019 Feb 21. Epub 2019 Feb 21.

Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark Odense, Odense, Denmark; Dept. of Pathology, Odense University Hospital, Odense, Denmark.

Mosaic genome-wide paternal uniparental disomy (GW-pUPD) is a rarely recognised disorder. The phenotypic manifestations of multilocus imprinting defects (MLIDs) remain unclear. We report of an apparently non-syndromic infant with severe congenital hyperinsulinism (CHI) and diffuse pancreatic labelling by 18F*-DOPA-PET/CT leading to near-total pancreatectomy. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.02.004DOI Listing
February 2019
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Hypertension in Potocki-Shaffer syndrome: A case report.

Eur J Med Genet 2019 Feb 20. Epub 2019 Feb 20.

Baylor College of Medicine, Department of Pediatrics, USA; Baylor College of Medicine, Renal Section, Department of Pediatrics, and Texas Children's Hospital, USA. Electronic address:

Potocki-Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome caused by heterozygous deletion of 11p11.2p12. Typical features described in patients with PSS include developmental delay, intellectual disability, multiple cartilaginous exostoses, biparietal foramina, craniofacial abnormalities, and genitourinary anomalies. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.02.005DOI Listing
February 2019
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A compound heterozygosity of Tecrl gene confirmed in a catecholaminergic polymorphic ventricular tachycardia family.

Eur J Med Genet 2019 Feb 18. Epub 2019 Feb 18.

Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University, No. 355 Luding Road, Shanghai, 200062, China. Electronic address:

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the most common causes of sudden cardiac death (SCD) during childhood and in adolescence. Trans-2, 3-enoyl-CoA reductase-like (Tecrl) gene mutations (Arg196Gln and c.331+1G > A splice site mutation) were first reported in CPVT. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.018DOI Listing
February 2019
2 Reads

ATM mutation spectrum in Russian children with ataxia-telangiectasia.

Eur J Med Genet 2019 Feb 14. Epub 2019 Feb 14.

St.-Petersburg Pediatric Medical University, St.-Petersburg, Russia; N.N. Petrov Institute of Oncology, St.-Petersburg, Russia; I.I. Mechnikov North-Western Medical University, St.-Petersburg, Russia; St.-Petersburg State University, St.-Petersburg, Russia.

Ataxia-telangiectasia (AT) is a severe autosomal recessive orphan disease characterized by a number of peculiar clinical manifestations. Genetic diagnosis of AT is complicated due to a large size of the causative gene, ATM. We used next-generation sequencing (NGS) technology for the ATM analysis in 17 children with the clinical diagnosis of AT. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.02.003DOI Listing
February 2019
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Antiepileptic therapy approaches in KCNQ2 related epilepsy: A systematic review.

Eur J Med Genet 2019 Feb 14. Epub 2019 Feb 14.

Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Dr. von Haunersches Children's Hospital, LMU Munich, Lindwurmstraße4, 80337, Munich, Germany; Comprehensive Epilepsy Center for Children, Adolescents and Adults, LMU Munich, Lindwurmstraße 4, 80337, Munich, Germany. Electronic address:

Background: KCNQ2 related disorders comprise both benign seizure disorders and early onset epileptic encephalopathies. Especially within the latter group, patients suffer from refractory seizures to standard antiepileptic drugs and developmental delay. Besides the hope of personalized medical approaches to treat the recently unraveled large amount of genetic channelopathies, there are sparse systematic data on treatment responses in KCNQ2 related epilepsy in larger cohorts. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183066
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http://dx.doi.org/10.1016/j.ejmg.2019.02.001DOI Listing
February 2019
15 Reads

Leukoencephalopathy in RIN2 syndrome: Novel mutation and expansion of clinical spectrum.

Eur J Med Genet 2019 Feb 13. Epub 2019 Feb 13.

Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

RIN2 syndrome also known as MACS syndrome is a rare autosomal recessive connective tissue disorder caused by RIN2 mutations and is accompanied by following clinical features: macrocephaly, coarsening of facial features, downward slanting palpebral fissures, Puffy droopy eyelids, full everted lips, soft redundant skin especially in face, gum hypertrophy, irregular dentition, sparse scalp hair, skeletal problems, joint hypermobility and scoliosis. RIN2 gene encodes the RAS and RAB interactor 2 and biallelic mutations in this gene cause cell trafficking dysfunction. Here we reported the eleventh patient of RIN2 syndrome in a 4 yr-old boy, from Tehran, Iran as the youngest reported patient so far. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.02.002DOI Listing
February 2019
1 Read

MEIS2 gene is responsible for intellectual disability, cardiac defects and a distinct facial phenotype.

Eur J Med Genet 2019 Feb 5. Epub 2019 Feb 5.

Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Myeloid ecotropic insertion site 2 (MEIS2) gene, encoding a homeodomain-containing transcription factor, has been recently related to syndromic intellectual disability with cleft palate and cardiac defects. Here, we present a male patient, aged 10, with cardiac defects, intellectual disability, facial dysmorphisms and gastroesophageal reflux. Whole exome sequencing revealed a novel de novo nonsense mutation in the MEIS2 gene. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.017DOI Listing
February 2019
4 Reads

A novel RAD21 mutation in a boy with mild Cornelia de Lange presentation: Further delineation of the phenotype.

Eur J Med Genet 2019 Feb 2. Epub 2019 Feb 2.

Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano, via Ariosto 13, 20145, Milan, Italy.

Cornelia de Lange syndrome is a rare autosomal dominant or X-linked developmental disorder characterized by characteristic facial dysmorphism, intellectual disability, growth retardation, upper limb and multiorgan anomalies. Causative mutations have been identified in five genes coding for the cohesion complex structure components or regulatory elements. Among them, RAD21 is associated with a milder phenotype. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.010DOI Listing
February 2019
1 Read

WDR11 is another causative gene for coloboma, cardiac anomaly and growth retardation in 10q26 deletion syndrome.

Eur J Med Genet 2019 Jan 31. Epub 2019 Jan 31.

Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. Electronic address:

10q26 deletion syndrome is caused by a rare chromosomal abnormality, and patients with this syndrome present with an extensive and heterogeneous phenotypic spectrum. Several genes, such as EMX2 and FGFR2, were identified as the cause genital anomalies and facial dysmorphism in 10q26 deletion syndrome. However, the critical region for 10q26 deletion syndrome is not determined and the precise relationships between the causative genes and the phenotypes are still controversial. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.016DOI Listing
January 2019
4 Reads

De-novo mutations in patients with chronic ultra-refractory epilepsy with onset after age five years.

Eur J Med Genet 2019 Jan 31. Epub 2019 Jan 31.

Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Ireland; The FutureNeuro Research Centre, RCSI, Dublin, Ireland. Electronic address:

We set out to investigate whether a de-novo paradigm could explain genetic causes of chronic ultra-refractory epilepsy, with onset later than the typical age for the epileptic encephalopathies. We performed exome sequencing on nine adult patients with MRI-negative epilepsy and no preceding intellectual disability. All had an onset of seizures after five years old and had chronic ultra-refractory epilepsy defined here as having failed more than six anti-epileptic drugs and currently experiencing ≥4 disabling seizures per month. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.015DOI Listing
January 2019
2 Reads

Novel variant in the KCNK9 gene in a girl with Birk Barel syndrome.

Eur J Med Genet 2019 Jan 25. Epub 2019 Jan 25.

Department of Paediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic.

Birk Barel syndrome also known as KCNK9 imprinting syndrome is a rare developmental disorder associated with a loss-of-function variant in KCNK9, an imprinted gene with maternal expression on the 8th chromosome encoding the TASK3 (TWIK-related acidity inhibited K + -channel 3). Only two variants of KCNK9 have been associated with this condition before, both of them leading to the same amino-acid exchange p.Gly236Arg (Barel ´ 2008, Graham ´ 2016). Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.009DOI Listing
January 2019

Biallelic loss of function variants in ATP1A2 cause hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations.

Eur J Med Genet 2019 Jan 25. Epub 2019 Jan 25.

Mendelics Genomic Analysis, CEP 04013-000, São Paulo, SP, Brazil; Neurogenetics, Neurology Department, Hospital das Clínicas da Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address:

The Na/K- ATPase acts as an ion pump maintaining the essential plasma membrane potential in all mammalian cell types, and is essential for many cellular functions. There are four α isoforms (α1, α2, α3 and α4) with distinct expression patterns, kinetic properties and substrate affinity. The α2-isoform is encoded by ATP1A2 and evidence supports its utmost importance in Cl homeostasis in neurons, and in the function of respiratory neurons at birth. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.014DOI Listing
January 2019

Expanded PCH1D phenotype linked to EXOSC9 mutation.

Eur J Med Genet 2019 Jan 25. Epub 2019 Jan 25.

Pediatric Department, Latifa Hospital, Dubai Health Authority, P.O.Box 4115, Dubai, United Arab Emirates.

Pontocerebellar Hypoplasia type 1 is a rare heterogeneous neurodegenerative disorder with multiple subtypes linked to dysfunction of the exosome complex. Patients with mutations in exosome subunits exhibit a generally lethal phenotype characterized by cerebellar and pontine hypoplasia in association with spinal motor neuropathy and multiple systemic and neurologic features. Recently, two variants in the novel PCH1 associated protein EXOSC9 p. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.012DOI Listing
January 2019
3 Reads
1.486 Impact Factor

Small interstitial 9p24.3 deletions principally involving KANK1 are likely benign copy number variants.

Eur J Med Genet 2019 Jan 23. Epub 2019 Jan 23.

Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia; Victorian Clinical Genetics Service, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia; Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Melbourne, Australia.

A small heterozygous deletion involving KANK1 was originally reported in 2005 to cause cerebral palsy in one large Israeli family of Jewish Moroccan origin. There were nine affected children over two generations to five unaffected fathers. All of these children had congenital hypotonia that evolved into spastic quadriplegia over the first year of life, along with intellectual impairment and brain atrophy. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.008DOI Listing
January 2019
2 Reads

Whole-exome sequencing identifies rare compound heterozygous mutations in the MSTO1 gene associated with cerebellar ataxia and myopathy.

Eur J Med Genet 2019 Jan 24. Epub 2019 Jan 24.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Human MSTO1 is involved in the regulation of mitochondrial distribution and morphology and its unregulated expression leads to mitochondrial disorder. Despite its significance for mitochondrial functions, human MSTO1 gene is rarely studied before 2017. As of late, MSTO1 mutations have been reported to cause clinical manifestations such as myopathy, cerebellar atrophy and ataxia, motor developmental delay, and pigmentary retinopathy. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.013DOI Listing
January 2019
1 Read

Primary coenzyme Q10 Deficiency-6 (COQ10D6): Two siblings with variable expressivity of the renal phenotype.

Eur J Med Genet 2019 Jan 22. Epub 2019 Jan 22.

Istanbul University, Istanbul Faculty of Medicine, Pediatric Nephrology Department, Istanbul, Turkey.

Primary coenzyme Q10 deficiency-6 (COQ10D6) is a rare autosomal recessive disorder caused by COQ6 mutations. The main clinical manifestations are infantile progressive nephrotic syndrome (NS) leading to end-stage renal disease and sensorineural deafness. A 7-year-old girl was diagnosed with steroid-resistant NS (SRNS) and an audiological work-up revealed bilateral sensorineural deafness. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.011DOI Listing
January 2019
7 Reads

Heterotopic ossifications and Charcot joints: Congenital insensitivity to pain with anhidrosis (CIPA) and a novel NTRK1 gene mutation.

Eur J Med Genet 2019 Jan 21. Epub 2019 Jan 21.

Institute of Human Genetics, Medical Center of the Johannes Gutenberg University Mainz, University of Mainz, Germany.

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN-IV), is a rare and severe autosomal recessive disorder. We report on an adult female patient whose clinical findings during childhood were not recognized as CIPA. There was neither complete anhidrosis nor a recognizable sensitivity to heat. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.003DOI Listing
January 2019
4 Reads

Oligo-astrocytoma in LZTR1-related Noonan syndrome.

Eur J Med Genet 2019 Jan 19. Epub 2019 Jan 19.

Department of Genetics, APHP-Robert DEBRE University Hospital, Denis Diderot School of Medicine, Paris University, France; INSERM UMR1141, Paris, France. Electronic address:

Mutations in LZTR1, already known to be causal in familial schwannomatosis type 2, have been recently involved in a small proportion of patients with autosomal dominant and autosomal recessive Noonan syndrome. LZTR1 is also a driver gene in non syndromal glioblastoma. We report a 26-year-old patient with typical Noonan syndrome, and the dominantly transmitted c. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.007DOI Listing
January 2019
8 Reads

Understanding attitudes and behaviors towards cell-free DNA-based noninvasive prenatal testing (NIPT): A survey of European health-care providers.

Eur J Med Genet 2019 Jan 14. Epub 2019 Jan 14.

Prenatal Genetic Diagnosis Unit, Genetic Institute, Tel Aviv Medical Center, Tel Aviv, Israel. Electronic address:

Cell-free DNA-based noninvasive prenatal testing (cfDNA) is a relatively new screening tool that analyzes cfDNA circulating in maternal plasma to screen for aneuploidies. Since its introduction, cfDNA has been rapidly adopted by health care providers (HCPs). This rapid adoption, as well as progressive developments in the technology, requires professional societies to continuously update their guidelines to indicate the broadening scope both in terms of test indications and patient populations for whom it has become the appropriate primary test. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183071
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http://dx.doi.org/10.1016/j.ejmg.2019.01.006DOI Listing
January 2019
11 Reads

Pediatric endocrinology through syndromes.

Eur J Med Genet 2019 Jan 14. Epub 2019 Jan 14.

Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; University of Trieste, Trieste, Italy.

In everyday practice, a pediatric endocrinologist will face a variety of different endocrine issues (such as short or tall stature, dysthyroidism, abnormal pubertal timing or impaired glucose metabolism), which relevantly contribute to the global care of a number of syndromic conditions. On the other hand, the presence of endocrine features may assist in the diagnostic process, leading to final diagnosis of a syndromic disorder. The intention of this review is to provide a referenced overview of different genetic syndromes characterized by endocrine features, and to present a possible classification, based on whether the endocrinopathy or the syndrome is typically recognized first. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.004DOI Listing
January 2019
12 Reads

A de novo TBX3 mutation presenting as dorsalization of the little fingers: A forme fruste phenotype of ulnar-mammary syndrome.

Eur J Med Genet 2019 Jan 14. Epub 2019 Jan 14.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. Electronic address:

Ulnar-mammary syndrome (UMS) is a rare syndromic limb malformation caused by heterozygous mutations in TBX3. The name highlights the two commonly involved body parts i.e. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.005DOI Listing
January 2019
2 Reads

Renal disease in Cockayne syndrome.

Eur J Med Genet 2019 Jan 7. Epub 2019 Jan 7.

Service de Pédiatrie 1, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address:

Background: Cockayne Syndrome (CS) is a rare autosomal recessive multi-systemic disorder, characterized; by developmental delay, microcephaly, severe growth failure and sensorial impairment. Renal complications have been reported but remain underinvestigated. The objective of this study was to perform a review of renal disease in a cohort of CS patients. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.01.002DOI Listing
January 2019
5 Reads

Microdeletion and microduplication of 1p36.11p35.3 involving AHDC1 contribute to neurodevelopmental disorder.

Eur J Med Genet 2019 Jan 4. Epub 2019 Jan 4.

Dongguan Maternal and Child Health Care Hospital, Dongguan, 523120, China; Dongguan Institute of Reproductive and Genetic Research, Dongguan, 523120, China. Electronic address:

Xia-Gibbs syndrome is a rare genetic condition characterized by intellectual disability, growth retardation, delayed psychomotor development with absent or poor expressive language, distinctive facial features, hypotonia, laryngomalacia and obstructive sleep apnea. At present, Xia-Gibbs syndrome has been reported to be mainly caused by truncating mutations in AHDC1 gene located on chromosome 1p36.11. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183041
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http://dx.doi.org/10.1016/j.ejmg.2019.01.001DOI Listing
January 2019
8 Reads

CNV analysis using whole exome sequencing identified biallelic CNVs of VPS13B in siblings with intellectual disability.

Eur J Med Genet 2018 Dec 30. Epub 2018 Dec 30.

Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Japan; Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan. Electronic address:

Cohen syndrome is an autosomal recessive disease characterized by myopia, retinal dystrophy, neutropenia, short stature, microcephaly, persistent hypotonia, intellectual disability (ID), and a distinct facial appearance. Cohen syndrome is caused by mutations, such as single nucleotide variants (SNVs) and small insertions/deletions, and copy number variations (CNVs) in vacuolar protein sorting 13 homolog B (VPS13B). Here, we report Japanese siblings with ID, who were subsequently diagnosed with Cohen syndrome by whole exome sequencing (WES). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183015
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http://dx.doi.org/10.1016/j.ejmg.2018.12.015DOI Listing
December 2018
3 Reads

"There is a chance for me" - Risk communication in advanced maternal age genetic counseling sessions in South Africa.

Eur J Med Genet 2018 Dec 30. Epub 2018 Dec 30.

Communication and Information Science, Rijksuniversiteit Groningen, Groningen, the Netherlands.

Providing risk information is central to genetic counseling. Many studies have examined risk communication, but the focus has been on professional and patient perspectives. Less information is available on risk communication in interactions. Read More

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http://dx.doi.org/10.1016/j.ejmg.2018.12.014DOI Listing
December 2018
1 Read

Oro-dental and cranio-facial characteristics of osteogenesis imperfecta type V.

Eur J Med Genet 2018 Dec 26. Epub 2018 Dec 26.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Osteogenesis imperfecta (OI) type V is an ultrarare heritable bone disorder caused by the heterozygous c.-14C > T mutation in IFITM5. The oro-dental and craniofacial phenotype has not been described in detail, which we therefore undertook to evaluate in a multicenter study (Brittle Bone Disease Consortium). Read More

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http://dx.doi.org/10.1016/j.ejmg.2018.12.011DOI Listing
December 2018
4 Reads

Popular culture and genetics; friend, foe or something more complex?

Eur J Med Genet 2018 Dec 24. Epub 2018 Dec 24.

Wellcome Genome Campus Society and Ethics Research and Faculty of Education, University of Cambridge, United Kingdom.

While many people enjoy popular culture, these transactional experiences may not translate into formal or academic learning about a subject. In education and science communication settings popular culture is often presented as a source of inaccurate information about science. Different publics are often positioned as, at best, undiscriminating consumers and at worst victims of distorted scientific information. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183040
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http://dx.doi.org/10.1016/j.ejmg.2018.12.005DOI Listing
December 2018
13 Reads

Hypopigmented patches in Roberts/SC phocomelia syndrome occur via aneuploidy susceptibility.

Eur J Med Genet 2018 Dec 24. Epub 2018 Dec 24.

Department of Medical Genetics, Faculty of Medicine, Gazi University, Ankara, Turkey. Electronic address:

Roberts/SC phocomelia syndrome (RBS/SC) is a rare autosomal recessive inherited condition characterized by prenatal-onset growth retardation, craniofacial anomalies, and symmetrical limb reduction defects. Here, we present two affected siblings with RBS/SC who have consanguineous parents. Both patients had intrauterine growth retardation; similar facial findings, including arched eyebrows, epicanthic folds, posteriorly angulated ears, and retrognathia; and hypopigmented patches on their skin. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183016
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http://dx.doi.org/10.1016/j.ejmg.2018.12.013DOI Listing
December 2018
2 Reads

Char Syndrome a novel mutation and new insights: A clinical report.

Eur J Med Genet 2018 Dec 21. Epub 2018 Dec 21.

Medical Genetics Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Lebanon; Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Lebanon. Electronic address:

Transcription Factor AP-2 Beta (TFAP2B) functions in the differentiation of neural crest cell derivatives and contributes to the embryogenesis of the ductus arteriosus. Mutations of TFAP2B produces Char syndrome. Char syndrome is an autosomal dominant disorder comprising facial dysmorphism, hand anomalies, and patent ductus arteriosus (PDA). Read More

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http://dx.doi.org/10.1016/j.ejmg.2018.12.012DOI Listing
December 2018
2 Reads

Blurring boundaries. Interviews with PGT couples about comprehensive chromosome screening.

Eur J Med Genet 2018 Dec 17. Epub 2018 Dec 17.

UZ Brussel, Centrum Medische Genetica, Laarbeeklaan 101, 1090, Brussel, Belgium. Electronic address:

Objective: Comprehensive chromosome examination is a promising approach to Preimplantation Genetic Testing (PGT). Next to testing of specific chromosomes, such as in the case of reduced fertility due to chromosomal translocations, it allows testing of all chromosomes. Hence it potentially reduces the time to pregnancy and the risk of miscarriage. Read More

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http://dx.doi.org/10.1016/j.ejmg.2018.12.009DOI Listing
December 2018
2 Reads

CAPN1 mutations: Expanding the CAPN1-related phenotype: From hereditary spastic paraparesis to spastic ataxia.

Eur J Med Genet 2018 Dec 17. Epub 2018 Dec 17.

Department of Medicine (Neurology), University of Alberta, Edmonton, Canada; Departments of Medical Genetics and Pediatrics, University of Alberta, Edmonton, Canada.

Aims And Objective: To characterize the phenotype of CAPN1 (SPG76) mutations in patients diagnosed with hereditary spastic paraplegia (HSP).

Background: The CAPN1 gene, located on chromosome 11q13.1, is a protein-coding gene involved in neuronal plasticity, migration, microtubular regulation and cerebellar development. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183041
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http://dx.doi.org/10.1016/j.ejmg.2018.12.010DOI Listing
December 2018
3 Reads