8,481 results match your criteria American journal of medical genetics. Part A[Journal]


Further expanding the mutational spectrum and investigation of genotype-phenotype correlation in 3M syndrome.

Am J Med Genet A 2019 Apr 13. Epub 2019 Apr 13.

Department of Pediatric Genetics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

3M syndrome is characterized by severe pre- and postnatal growth retardation, typical facial features, and normal intelligence. Homozygous or compound heterozygous mutations in either CUL7, OBSL1, or CCDC8 have been identified in the etiology so far. Clinical and molecular features of 24 patients (23 patients and a fetus) from 19 unrelated families with a clinical diagnosis of 3M syndrome were evaluated and genotype-phenotype correlations were investigated with the use of DNA sequencing, chromosomal microarray, and whole exome sequencing accordingly. Read More

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http://dx.doi.org/10.1002/ajmg.a.61154DOI Listing

Autosomal recessive Treacher Collins syndrome due to POLR1C mutations: Report of a new family and review of the literature.

Am J Med Genet A 2019 Apr 8. Epub 2019 Apr 8.

Service de Génétique Médicale, CHU Nantes, Nantes, France.

Treacher Collins syndrome (TCS) is a frequent cause of mandibulofacial dysostosis. To date, TCS-causing mutations in three genes, namely TCOF1, POLR1D, and POLR1C have been identified. TCS is usually inherited in an autosomal dominant manner, with a high clinical variability and no phenotype-genotype correlation. Read More

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http://dx.doi.org/10.1002/ajmg.a.61147DOI Listing

TMEM70 deficiency: Novel mutation and hypercitrullinemia during metabolic decompensation.

Am J Med Genet A 2019 Apr 4. Epub 2019 Apr 4.

National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.

Respiratory chain disorders comprise a heterogeneous group of diseases that are the result of mutations in nuclear or mitochondrial genes. TMEM70 encodes a nuclear protein involved in the assembly of respiratory chain complex V. Although mutations in various genes can result in isolated complex V deficiency; TMEM70 mutations represent the most common reported etiology. Read More

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http://dx.doi.org/10.1002/ajmg.a.61138DOI Listing
April 2019
3 Reads

Status dystonicus, hyperpyrexia, and acute kidney injury in a patient with SOX2-anophthalmia syndrome.

Am J Med Genet A 2019 Apr 4. Epub 2019 Apr 4.

Division of Critical Care, Department of Pediatrics, Saint Louis University and Cardinal Glennon Children's Hospital, St. Louis, Missouri.

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http://dx.doi.org/10.1002/ajmg.a.61144DOI Listing
April 2019
2 Reads

Factors related to survival discharge in trisomy 18: A retrospective multicenter study.

Am J Med Genet A 2019 Apr 3. Epub 2019 Apr 3.

Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan.

Infants with trisomy 18 (T18) previously had a poor prognosis; however, the intensive care of these patients has markedly diversified the prognosis. We investigated the current situation of patients with T18, clarified factors for survival discharge, and surveyed actual home healthcare. A total of 117 patients with T18 admitted to nine institutions between 2000 and 2015 were retrospectively investigated. Read More

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http://dx.doi.org/10.1002/ajmg.a.61146DOI Listing
April 2019
8 Reads

Maladaptive behaviors in individuals with Angelman syndrome.

Am J Med Genet A 2019 Apr 3. Epub 2019 Apr 3.

Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Maladaptive behaviors are challenging and a source of stress for caregivers of individuals with Angelman Syndrome (AS). There is limited information on how these maladaptive behaviors vary over time among individuals with AS due to different genetic etiologies. In this study, caregivers of 301 individuals with AS were asked questions about their child's behavior and completed the Aberrant Behavior Checklist-Community version (ABC-C). Read More

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http://dx.doi.org/10.1002/ajmg.a.61140DOI Listing
April 2019
1 Read

Constitutive activation of the PI3K-AKT pathway and cardiovascular abnormalities in an individual with Kosaki overgrowth syndrome.

Am J Med Genet A 2019 Apr 2. Epub 2019 Apr 2.

Division of Cardiology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California.

Kosaki overgrowth syndrome is a recently described syndrome characterized by distinctive facial features, brain white matter lesions, and developmental delay. Germline activating heterozygous PDGFRB mutations have been reported in this condition. Systemic connective tissue-type findings have been described in some individuals. Read More

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http://dx.doi.org/10.1002/ajmg.a.61145DOI Listing

PIEZO2 deficiency is a recognizable arthrogryposis syndrome: A new case and literature review.

Am J Med Genet A 2019 Apr 2. Epub 2019 Apr 2.

Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.

PIEZO2 encodes a mechanically activated cation channel, which is abundantly expressed in dorsal root ganglion neuron and sensory endings of proprioceptors required for light touch sensation and proprioception in mice. Biallelic loss-of-function mutations in PIEZO2 (i.e. Read More

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http://dx.doi.org/10.1002/ajmg.a.61142DOI Listing
April 2019
2 Reads

Variants in the transcriptional corepressor BCORL1 are associated with an X-linked disorder of intellectual disability, dysmorphic features, and behavioral abnormalities.

Am J Med Genet A 2019 May 2;179(5):870-874. Epub 2019 Apr 2.

Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.

BCORL1, a transcriptional corepressor, is involved in negative gene regulation through associations with several protein complexes including Class II histone deacetylases (HDACs). Acquired somatic mutations in BCORL1 have been implicated in the pathogenesis of several malignancies, but germline mutations of BCORL1 have not been associated with a specific genetic syndrome. We report five individuals from three pedigrees with phenotypes including intellectual disability, behavioral difficulties, and dysmorphic features who were found via whole exome sequencing to have variants in BCORL1. Read More

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http://dx.doi.org/10.1002/ajmg.a.61118DOI Listing
May 2019
2 Reads

Distal arthrogryposis type 5 and PIEZO2 novel variant in a Canadian family.

Am J Med Genet A 2019 Apr 1. Epub 2019 Apr 1.

Paediatric Neurology Department, Children's Hospital, London Health Science Centre, London, Ontario, Canada.

The group of distal arthrogryposis (DA) disorders is characterized by congenital contractures of the distal joints. In most instances, these are genetic disorders are inherited in an autosomal dominant fashion; however, there is wide genetic and phenotypic spectrum. Distal arthrogryposis type 5 (DA5) is clinically characterized by short stature, deep-set eyes, ptosis, ophthalmoplegia, triangular facies, restrictive pulmonary function, and "firm" muscles. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61143
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http://dx.doi.org/10.1002/ajmg.a.61143DOI Listing
April 2019
3 Reads

Experiences of children with trisomy 18 referred to pediatric palliative care services on two continents.

Am J Med Genet A 2019 Apr 1. Epub 2019 Apr 1.

Louis Dundas Centre for Children's Palliative Care, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.

Children with trisomy 18 that survive beyond the neonatal period have multiple congenital anomalies, neurodevelopmental disability, and high mortality rates. The experience of children with trisomy 18 who receive pediatric palliative care services is largely unknown. We conducted a retrospective review of children with trisomy 18 receiving pediatric palliative care services at both Boston Children's Hospital, USA and Great Ormond Street Hospital, UK from January 1, 2004 to January 1, 2015. Read More

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http://dx.doi.org/10.1002/ajmg.a.61149DOI Listing

The final demise of Rodriguez lethal acrofacial dysostosis: A case report and review of the literature.

Am J Med Genet A 2019 Mar 28. Epub 2019 Mar 28.

Clinical Genetics Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

We evaluated a newborn with acrofacial dysostosis in whom a clinical diagnosis of Nager syndrome was entertained. Radiographs revealed hypoplasia of the scapulae and bilateral humeroradial synostosis, with absent ulna on the left and hypoplastic ulna on the right. The finding of bilateral humeroradial synostosis had not been seen in cases of Nager syndrome before and we considered other diagnoses. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61121
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http://dx.doi.org/10.1002/ajmg.a.61121DOI Listing
March 2019
2 Reads

Extracutaneous manifestations in phacomatosis cesioflammea and cesiomarmorata: Case series and literature review.

Am J Med Genet A 2019 Mar 28. Epub 2019 Mar 28.

Department of Pediatrics, Stanford School of Medicine, Stanford, California.

Phacomatosis pigmentovascularis (PPV) comprises a family of rare conditions that feature vascular abnormalities and melanocytic lesions that can be solely cutaneous or multisystem in nature. Recently published work has demonstrated that both vascular and melanocytic abnormalities in PPV of the cesioflammea and cesiomarmorata subtypes can result from identical somatic mosaic activating mutations in the genes GNAQ and GNA11. Here, we present three new cases of PPV with features of the cesioflammea and/or cesiomarmorata subtypes and mosaic mutations in GNAQ or GNA11. Read More

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http://dx.doi.org/10.1002/ajmg.a.61134DOI Listing

Mandibuloacral dysplasia with type B lipodystrophy in a patient from Chile.

Am J Med Genet A 2019 Mar 28. Epub 2019 Mar 28.

Génétique Humaine, Faculté de médecine, Université de Lorraine, Nancy, France.

We report the first case of mandibuloacral dysplasia with type B lipodystrophy (MADB) in Chile, South America. MADB is a very rare illness, characterized by short stature, mandibular hypoplasia, acro-osteolysis in hands, feet and clavicles, lipodystrophy, changes in skin pigments and skin calcinosis at knees and hands. Diagnosis was confirmed by molecular study that showed two compound heterozygous variants in ZMPSTE24 gene, c. Read More

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http://dx.doi.org/10.1002/ajmg.a.61139DOI Listing
March 2019
1 Read

Fetal cardiomyopathy in neurofibromatosis type I: Novel phenotype and review of the literature.

Am J Med Genet A 2019 Mar 28. Epub 2019 Mar 28.

Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Neurofibromatosis type I (NF1) is a relatively common genetic disorder characterized by neurocutaneous lesions, neurofibromas, skeletal anomalies, iris hamartomas, and predisposition to other tumors. NF1 results from heterozygous loss-of-function mutations in neurofibromin (NF1), and diagnosis is most often made using clinical diagnostic criteria. Cardiac manifestations of NF1 include congenital heart disease (such as valvar pulmonary stenosis), left ventricular hypertrophy, and adult-onset pulmonary hypertension. Read More

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http://dx.doi.org/10.1002/ajmg.a.61123DOI Listing
March 2019
1 Read

Clinical exome sequencing in 509 Middle Eastern families with suspected Mendelian diseases: The Qatari experience.

Am J Med Genet A 2019 Mar 27. Epub 2019 Mar 27.

Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.

Background: Clinical exome sequencing (CES) is rapidly becoming the diagnostic test of choice in patients with suspected Mendelian diseases especially those that are heterogeneous in etiology and clinical presentation. Reporting large CES series can inform guidelines on best practices for test utilization, and improves accuracy of variant interpretation through clinically-oriented data sharing.

Methods: This is a retrospective series of 509 probands from Qatar who underwent singleton or trio CES either as a reflex or naïve (first-tier) test from April 2014 to December 2016 for various clinical indications. Read More

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http://dx.doi.org/10.1002/ajmg.a.61126DOI Listing

Introducing in AJMG Part A: Genetic Syndromes in Adults.

Am J Med Genet A 2019 Mar 26. Epub 2019 Mar 26.

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.

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http://dx.doi.org/10.1002/ajmg.a.61141DOI Listing

Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil.

Am J Med Genet A 2019 Mar 26. Epub 2019 Mar 26.

Nupad - Center for Newborn Screening and Genetic Diagnostics, UFMG - Federal University of Minas Gerais, Belo Horizonte, Brazil.

Biotinidase deficiency is an autosomal recessive inherited metabolic disorder caused by mutations in the BTD gene. Clinical manifestations can be treated and effectively prevented with pharmacological doses of biotin. Nine novel mutations in BTD are reported in 14 children diagnosed by the newborn screening program in Minas Gerais, Brazil, from June 2013 to December 2017. Read More

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http://dx.doi.org/10.1002/ajmg.a.61137DOI Listing

Biallelic novel missense HHAT variant causes syndromic microcephaly and cerebellar-vermis hypoplasia.

Am J Med Genet A 2019 Mar 26. Epub 2019 Mar 26.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

We report two siblings with microcephaly, early infantile onset seizures, and cerebellar vermis hypoplasia, in whom whole exome sequencing revealed a novel homozygous missense (c.770T>C, p.[Leu257Pro]) variant in the hedgehog acyl-transferase gene (HHAT), encoding an enzyme required for the attachment of palmitoyl residues that are critical for multimerization and long and short range hedgehog signaling. Read More

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http://dx.doi.org/10.1002/ajmg.a.61133DOI Listing
March 2019
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Inferring parental gonadal mosaicism in LMNA-associated muscular dystrophy by ultra-deep next generation sequencing: A sensitive approach providing valuable information for genetic counseling.

Am J Med Genet A 2019 Mar 26. Epub 2019 Mar 26.

Consultorio de Neurogenética, Centro Universitario de Neurología y División Neurología, Hospital J.M. Ramos Mejía, Facultad de Medicina, UBA, Buenos Aires, Argentina.

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http://dx.doi.org/10.1002/ajmg.a.61135DOI Listing

First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and advances of new therapeutics.

Am J Med Genet A 2019 Mar 25. Epub 2019 Mar 25.

Institute of Medical Genetics, Cardiff University, Cardiff, United Kingdom.

The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio-facio-cutaneous syndrome, Legius syndrome, capillary malformation arterio-venous malformation syndrome, and SYNGAP1 autism. Read More

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http://dx.doi.org/10.1002/ajmg.a.61125DOI Listing
March 2019
1 Read
2.159 Impact Factor

From process to progress-2017 International Conference on Neurofibromatosis 1, Neurofibromatosis 2 and Schwannomatosis.

Am J Med Genet A 2019 Mar 25. Epub 2019 Mar 25.

Division of Neuroscience, Oregon National Primate Research Center, and Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, Oregon.

The neurofibromatoses are inherited, tumor suppressor disorders that are characterized by multiple, benign peripheral nerve sheath tumors and other nervous system tumors. Each disease is associated with a distinct genetic mutation and with a different pathogenesis and clinical course. Neurofibromatosis 1 (NF1) is common and epitomized by multiple neurofibromas with widespread complications. Read More

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http://dx.doi.org/10.1002/ajmg.a.61112DOI Listing
March 2019
2 Reads

Orofacial clefts in California: No decline in Alberta, Canada.

Am J Med Genet A 2019 Mar 25. Epub 2019 Mar 25.

Alberta Congenital Anomalies Surveillance System, Clinical Genetics, Alberta Health Services, Calgary, Alberta, Canada.

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http://dx.doi.org/10.1002/ajmg.a.61136DOI Listing

A Japanese patient with RAD51-associated Fanconi anemia.

Am J Med Genet A 2019 Mar 25. Epub 2019 Mar 25.

Department of Pediatrics, University of Tokyo, Tokyo, Japan.

RAD51 is the only identified autosomal dominant gene to date causative of Fanconi anemia (FA) due to dominant negative effects. Only two patients with RAD51-associated FA have been reported with atypical FA phenotypes without bone marrow failure. We describe a new Asian patient with a novel RAD51 mutation, presenting with multiple congenital anomalies and atypical FA with chromosomal instability. Read More

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http://dx.doi.org/10.1002/ajmg.a.61130DOI Listing
March 2019
1 Read

Reported environmental exposures are inversely associated with obtaining a genetic diagnosis in the Undiagnosed Diseases Network.

Am J Med Genet A 2019 Mar 23. Epub 2019 Mar 23.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

The Undiagnosed Diseases Network (UDN) aims to achieve a unifying etiologic diagnosis for patients with mysterious conditions. Although the UDN has focused on the identification of genetic determinants, environmental etiologies may be causative or modifying agents that interact with predisposing genes. We developed and implemented a screening questionnaire to assess environmental exposures in UDN patients. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61132
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http://dx.doi.org/10.1002/ajmg.a.61132DOI Listing
March 2019
2 Reads

PADDAS syndrome associated with hair dysplasia caused by a de novo missense variant of PUM1.

Am J Med Genet A 2019 Mar 23. Epub 2019 Mar 23.

Department of Medical Genetics, CHU Bordeaux, Bordeaux, France.

PUM1 has been very recently reported as responsible for a new form of developmental disorder named PADDAS syndrome. We describe here an additional patient with early onset developmental delay, epilepsy, microcephaly, and hair dysplasia, with a de novo heterozygous missense variant of PUM1: c.3439C > T, p. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61127
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http://dx.doi.org/10.1002/ajmg.a.61127DOI Listing
March 2019
4 Reads

Ptosis as a unique hallmark for autosomal recessive WNT1-associated osteogenesis imperfecta.

Am J Med Genet A 2019 Mar 21. Epub 2019 Mar 21.

Department of Biomolecular Medicine, Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium.

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder, mainly characterized by bone fragility and low bone mass. Defects in the type I procollagen-encoding genes account for the majority of OI, but increasingly more rare autosomal recessive (AR) forms are being identified, which are caused by defects in genes involved in collagen metabolism, bone mineralization, or osteoblast differentiation. Bi-allelic mutations in WNT1 have been associated with a rare form of AR OI, characterized by severe osteoporosis, vertebral compression, scoliosis, fractures, short stature, and variable neurological problems. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61119
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http://dx.doi.org/10.1002/ajmg.a.61119DOI Listing
March 2019
15 Reads
2.159 Impact Factor

A novel pathogenic variant in OFD1 results in X-linked Joubert syndrome with orofaciodigital features and pituitary aplasia.

Am J Med Genet A 2019 Mar 20. Epub 2019 Mar 20.

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Orofaciodigital syndrome type I and X-linked recessive Joubert syndrome are known ciliopathic disorders that are caused by pathogenic variants in OFD1 gene. Endocrine system involvement with these conditions is not well described. We present the first report of a newborn male with a novel hemizygous variant in OFD1 gene c. Read More

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http://dx.doi.org/10.1002/ajmg.a.61018DOI Listing

Genotype-phenotype specificity in Menke-Hennekam syndrome caused by missense variants in exon 30 or 31 of CREBBP.

Am J Med Genet A 2019 Mar 20. Epub 2019 Mar 20.

Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

CREBBP loss-of function variants cause Rubinstein-Taybi syndrome (RTS). There have been two separate reports of patients with missense variants in exon 30 or 31 of CREBBP in individuals lacking the characteristic facial and limb dysmorphism associated with RTS. Frequent features in this condition include variable intellectual disability, short stature, autistic behavior, microcephaly, feeding problems, epilepsy, recurrent upper airway infections, and mild hearing impairment. Read More

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http://dx.doi.org/10.1002/ajmg.a.61131DOI Listing
March 2019
1 Read

Height growth velocity during infancy and childhood in achondroplasia.

Am J Med Genet A 2019 Mar 19. Epub 2019 Mar 19.

Growth and Development, Pediatric Garrahan Hospital, Buenos Aires, Argentina.

There is a lack of knowledge about longitudinal growth during childhood in achondroplasia. We report patterns of linear growth and height growth velocity references. The sample consisted of 84 children, 41 girls and 43 boys. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61120
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http://dx.doi.org/10.1002/ajmg.a.61120DOI Listing
March 2019
6 Reads
2.159 Impact Factor

11q24.2q24.3 microdeletion in two families presenting features of Jacobsen syndrome, without intellectual disability: Role of FLI1, ETS1, and SENCR long noncoding RNA.

Am J Med Genet A 2019 Mar 19. Epub 2019 Mar 19.

Service de Génétique Médicale, CHU Nantes, France.

This report presents two families with interstitial 11q24.2q24.3 deletion, associated with malformations, hematologic features, and typical facial dysmorphism, observed in Jacobsen syndrome (JS), except for intellectual disability (ID). Read More

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http://dx.doi.org/10.1002/ajmg.a.61113DOI Listing
March 2019
1 Read

A de novo mutation in DHD domain of SKI causing spina bifida with no craniofacial malformation or intellectual disability.

Am J Med Genet A 2019 Mar 18. Epub 2019 Mar 18.

Department of orthopaedic Surgery, Spine Center, Changzheng Hospital, Second Military Medical Univerisity, Shanghai 20003, People's Republic of China.

Shprintzen-Goldberg syndrome (SGS) is a rare systemic connective tissue disorder characterized by craniofacial, skeletal, and cardiovascular manifestations. It is associated with a significant risk of intellectual disability, a feature which distinguishes it from Marfan and Loeys-Dietz syndromes. SGS is mainly caused by mutations in the SKI gene, a repressor of TGF-β activity. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61088
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http://dx.doi.org/10.1002/ajmg.a.61088DOI Listing
March 2019
3 Reads
2.159 Impact Factor

The burden of rare diseases.

Am J Med Genet A 2019 Mar 18. Epub 2019 Mar 18.

National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.

The subject of rare disease numbers is rife with misconceptions, not just in websites and other layman's literature, but also in the medical literature. Various websites mention numbers that are not validated by any solid data, while in turn the medical literature cites the aforementioned websites as sources, thus perpetuating a number of myths about rare diseases and their burden. We review the existing literature on rare disease numbers, in an attempt to demystify the subject. Read More

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http://dx.doi.org/10.1002/ajmg.a.61124DOI Listing

Cornelia de Lange syndrome, related disorders, and the Cohesin complex: Abstracts from the 8th biennial scientific and educational symposium 2018.

Am J Med Genet A 2019 Mar 15. Epub 2019 Mar 15.

Research Department, Cornelia de Lange Syndrome Foundation, Avon, Connecticut.

Cornelia de Lange Syndrome (CdLS), due to mutations in genes of the cohesin protein complex, is described as a disorder of transcriptional regulation. Phenotypes in this expanding field include short stature, microcephaly, intellectual disability, variable facial features and organ involvement, resulting in overlapping presentations, including established syndromes and newly described conditions. Individuals with all forms of CdLS have multifaceted complications, including neurodevelopmental, feeding, craniofacial, and communication. Read More

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http://dx.doi.org/10.1002/ajmg.a.61108DOI Listing
March 2019
4 Reads

First case of Roma ethnic origin with Andermann syndrome: A novel frameshift mutation in exon 20 of SLC12A6 gene.

Am J Med Genet A 2019 Mar 13. Epub 2019 Mar 13.

Department of Pediatrics and Medical Genetics, Medical University, Plovdiv, Bulgaria.

Andermann syndrome (AS) is caused by mutation of SLC12A6 gene. It comprises severe progressive sensory and motor neuropathy with early onset, varying degree of agenesis of corpus callosum (ACC) and mental retardation. AS occurs occasionally among population outside the northeastern Quebec-Saguenay-Lac- St-Jean and Charlevoix regions, inhabited by French Canadians. Read More

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http://dx.doi.org/10.1002/ajmg.a.61110DOI Listing

CHRNG-related nonlethal multiple pterygium syndrome: Muscle imaging pattern and clinical, histopathological, and molecular genetic findings.

Am J Med Genet A 2019 Mar 14. Epub 2019 Mar 14.

Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Hospital Universitari Sant Joan de Deu, Barcelona, Spain.

Mutations in the CHRNG gene cause autosomal recessive multiple pterygium syndrome (MPS). Herein we present a long-term follow-up of seven patients with CHRNG-related nonlethal MPS and we compare them with the 57 previously published patients. The objective is defining not only the clinical, histopathological, and molecular genetic characteristics, but also the type and degree of muscle involvement on whole-body magnetic resonance imaging (WBMRI). Read More

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http://dx.doi.org/10.1002/ajmg.a.61122DOI Listing

Improved clinical outcome following liver transplant in patients with ethylmalonic encephalopathy.

Am J Med Genet A 2019 Mar 12. Epub 2019 Mar 12.

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

Ethylmalonic encephalopathy (EE) is a rapidly progressive autosomal recessive mitochondrial disease caused by biallelic pathogenic variants in the ETHE1 gene that encodes the mitochondrial sulfur dioxygenase. It is characterized by neurodevelopmental delay and regression, pyramidal and extrapyramidal signs, recurrent petechiae, chronic diarrhea, and orthostatic acrocyanosis. Laboratory findings include elevated serum levels of lactate and C4-C5 acylcarnitines, and elevated urinary excretion of ethylmalonic acid and C4-C6 acylglycines, notably isobutyrylglycine and 2-methylbutyrylglycine. Read More

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http://dx.doi.org/10.1002/ajmg.a.61104DOI Listing

Corrigendum to "The human phenotype of ornithine decarboxylase superactivity: a new syndrome".

Am J Med Genet A 2019 Apr 15;179(4):747-748. Epub 2019 Feb 15.

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http://dx.doi.org/10.1002/ajmg.a.61064DOI Listing

Acute leukemia in a patient with 15q overgrowth syndrome.

Am J Med Genet A 2019 Mar 12. Epub 2019 Mar 12.

Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, California.

Overgrowth syndromes are rare genetic conditions which present as global or segmental hyperplasia and are sometimes associated with increased risk of malignancy. Trisomy of the terminal portion of 15q which includes the IGFR1 gene, produces a rare overgrowth phenotype that has been termed 15q overgrowth syndrome (15q OGS). Upregulation of IGF1R has long been implicated in oncogenesis of multiple cancer types, including acute leukemias, and has been shown to render cells more susceptible to other transforming events. Read More

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http://dx.doi.org/10.1002/ajmg.a.61115DOI Listing
March 2019
6 Reads

Pain in individuals with RASopathies: Prevalence and clinical characterization in a sample of 80 affected patients.

Am J Med Genet A 2019 Mar 10. Epub 2019 Mar 10.

Department of Woman and Child Health, Center for Rare Diseases and Birth Defects, Institute of Pediatrics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Pain in individuals with RASopathies is a neglected topic in literature. In this article, we assessed prevalence and profile of pain in a sample of 80 individuals affected by RASopathies. The study sample included individuals with Noonan syndrome (N = 42), Costello syndrome (N = 17), and cardio-facio-cutaneous syndrome (N = 21). Read More

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http://dx.doi.org/10.1002/ajmg.a.61111DOI Listing
March 2019
4 Reads

Case report and novel treatment of an autosomal recessive Leigh syndrome caused by short-chain enoyl-CoA hydratase deficiency.

Am J Med Genet A 2019 May 7;179(5):803-807. Epub 2019 Mar 7.

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

Short chain enoyl-CoA hydratase (SCEH) deficiency leads to a severe form of autosomal recessive Leigh syndrome with inevitable neurological decline and early mortality. SCEH is most notably involved in valine catabolism, a deficiency of which results in various metabolic alterations, including increased levels of the highly reactive metabolite 2-methacrylyl-CoA. With no proven treatments available to date, it has been speculated that patients may respond to a valine restricted diet and/or N-acetylcysteine supplementation, as suggested by early studies of a very similar inborn error of metabolism, 3-hydroxyisobutyryl-CoA hydrolase deficiency. Read More

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http://dx.doi.org/10.1002/ajmg.a.61074DOI Listing
May 2019
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Genotype and phenotype correlation in 103 individuals with 2q37 deletion syndrome reveals incomplete penetrance and supports HDAC4 as the primary genetic contributor.

Am J Med Genet A 2019 May 7;179(5):782-791. Epub 2019 Mar 7.

Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.

The 2q37 deletion syndrome, also described in the literature as brachydactyly-mental retardation syndrome (MIM 600430), is caused by deletion or haploinsufficiency of the HDAC4 gene, which encodes the histone deacetylase 4 protein. Although the most commonly described hallmark features of the 2q37 deletion syndrome include brachydactyly type E, developmental delay, obesity, autistic features, and craniofacial or skeletal dysmorphism, a literature review of 101 published cases plus two newly reported individuals indicates that there is a high degree of variability in the presence of some of the features that are considered the most characteristic of the syndrome: overweight and obesity (34%), cognitive-behavioral issues (79%), dysmorphic craniofacial features (86%), and type E brachydactyly (48%). These features overlap with other neurodevelopmental conditions, including Smith-Magenis syndrome (SMS), and may be incompletely penetrant or demonstrate variable expressivity, depending on the specific chromosomal anomaly. Read More

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http://dx.doi.org/10.1002/ajmg.a.61089DOI Listing
May 2019
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SATB2-associated syndrome in patients from Japan: Linguistic profiles.

Am J Med Genet A 2019 Mar 7. Epub 2019 Mar 7.

Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.

Cleft palate can be classified as either syndromic or nonsyndromic. SATB2-associated syndrome is one example of a syndromic cleft palate that is accompanied by intellectual disability, and various dental anomalies. SATB2-associated syndrome can be caused by several different molecular mechanisms including intragenic mutations and deletions of SATB2. Read More

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http://dx.doi.org/10.1002/ajmg.a.61114DOI Listing
March 2019
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Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis.

Am J Med Genet A 2019 May 5;179(5):813-816. Epub 2019 Mar 5.

Regional Genetics Program, CHEO, University of Ottawa, Ottawa, Ontario, Canada.

Neu-Laxova syndrome (NLS) is a lethal autosomal recessive microcephaly syndrome associated with intrauterine growth restriction (IUGR) and multiple congenital anomalies. Clinical features include central nervous system malformations, joint contractures, ichthyosis, edema, and dysmorphic facial features. Biallelic pathogenic variants in either the PHGDH or PSAT1 genes have been shown to cause NLS. Read More

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http://dx.doi.org/10.1002/ajmg.a.61076DOI Listing
May 2019
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Patient with anomalous skin pigmentation expands the phenotype of ARID2 loss-of-function disorder, a SWI/SNF-related intellectual disability.

Am J Med Genet A 2019 May 5;179(5):808-812. Epub 2019 Mar 5.

Munroe-Meyer Institute for Genetics & Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska.

ARID2 loss-of-function is associated with a rare genetic disorder characterized in 14 reported patients to date. ARID2 encodes a member of the SWItch/sucrose non-fermentable chromatin remodeling complex. Other genes encoding subunits of this complex, such as ARID1A, ARID1B, and SMARCA2, are mutated in association with Coffin-Siris syndrome (CSS) and Nicolaides Baraitser syndrome (NCBRS) phenotypes. Read More

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http://doi.wiley.com/10.1002/ajmg.a.61075
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http://dx.doi.org/10.1002/ajmg.a.61075DOI Listing
May 2019
4 Reads