8,336 results match your criteria American Journal of Medical Genetics Part A[Journal]


Gynecologic health in cartilage-hair hypoplasia: A survey of 26 adult females.

Am J Med Genet A 2018 Dec 18. Epub 2018 Dec 18.

Children's Hospital, Pediatric Research Center, HUS, Helsinki University Hospital and Helsinki University, Helsinki, Finland.

Cartilage-hair hypoplasia (CHH) is a rare metaphyseal chondrodysplasia significantly affecting adult height and quality of life. Immunodeficiency and increased risk for malignancies contribute to significant morbidity. Little is known about gynecologic health in CHH. Read More

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http://dx.doi.org/10.1002/ajmg.a.60684DOI Listing
December 2018

Primary muscle involvement in a 15-year-old girl with the recurrent homozygous c.362dupC variant in FKBP14.

Am J Med Genet A 2018 Dec 18. Epub 2018 Dec 18.

Division of Neuromuscular and Neurodegenerative Disorders, IRCCS-Bambino Gesù Children's Hospital, Rome, Italy.

Kyphoscoliotic Ehlers-Danlos syndrome associated with FKBP14 (FKBP14-kEDS) is an ultrarare autosomal recessive disorder reported in less than 30 individuals so far. In its original description, emphasis was put on the mild muscle involvement. Further reports confirm that FKBP14-kEDS is distinguishable from primary muscle disorders by the lack of progressive muscle disease. Read More

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http://dx.doi.org/10.1002/ajmg.a.61006DOI Listing
December 2018

Novel VPS33B mutation in a patient with autosomal recessive keratoderma-ichthyosis-deafness syndrome.

Am J Med Genet A 2018 Dec 18. Epub 2018 Dec 18.

Institute of Clinical Genetics, Technische Universität Dresden, Dresden, Germany.

Autosomal recessive keratoderma-ichthyosis-deafness (ARKID) syndrome is a rare multisystem disorder caused by biallelic mutations in VPS33B; only three patients have been reported to date. ARKID syndrome is allelic to arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome (MIM #208085), a severe disorder with early lethality whose phenotypic characteristics also include ichthyosis, hearing loss, severe failure to thrive, platelet dysfunction and osteopenia. We report on an 11-year-old male patient with ARKID syndrome and compound heterozygous VPS33B mutations, one of which [c. Read More

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http://dx.doi.org/10.1002/ajmg.a.40634DOI Listing
December 2018

A novel case of Greenberg dysplasia and genotype-phenotype correlation analysis for LBR pathogenic variants: An instructive example of one gene-multiple phenotypes.

Am J Med Genet A 2018 Dec 18. Epub 2018 Dec 18.

Department of Medical Sciences, University of Torino, Torino, Italy.

Greenberg skeletal dysplasia is an autosomal recessive, perinatal lethal disorder associated with biallelic variants affecting the lamin B receptor (LBR) gene. LBR is also associated with the autosomal recessive anadysplasia-like spondylometaphyseal dysplasia, and the autosomal dominant Pelger-Huët anomaly, a benign laminopathy characterized by anomalies in the nuclear shape of blood granulocytes. The LBR is an inner nuclear membrane protein that binds lamin B proteins (LMNB1 and LMNB2), interacts with chromatin, and exerts a sterol reductase activity. Read More

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http://dx.doi.org/10.1002/ajmg.a.61000DOI Listing
December 2018

SCAPER-associated nonsyndromic autosomal recessive retinitis pigmentosa.

Am J Med Genet A 2018 Dec 18. Epub 2018 Dec 18.

Department of Ophthalmology, New York-Presbyterian Hospital, New York, New York.

Mutations in the gene SCAPER (S-phase CyclinA Associated Protein residing in the Endoplasmic Reticulum) have recently been identified as causing syndromic autosomal recessive retinitis pigmentosa with the extraocular manifestations of intellectual disability and attention-deficit/hyperactivity disorder. We present the case of an 11-year-old boy that presented to our clinic with the complaint of decreased night vision. Clinical presentation, family history, and diagnostic imaging were congruent with the diagnosis of autosomal recessive retinitis pigmentosa. Read More

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http://dx.doi.org/10.1002/ajmg.a.61001DOI Listing
December 2018

Terminal osseous dysplasia with pigmentary defects (TODPD) in a Turkish girl with new skin findings.

Am J Med Genet A 2018 Dec 18. Epub 2018 Dec 18.

Medical Genetics Department, Koç University School of Medicine (KUSoM), İstanbul, Turkey.

Terminal osseous dysplasia with pigmentary defects (TODPD; MIM #300244) is an extremely rare, X-linked dominant, in utero male-lethal disease, characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibromatosis of childhood. Delayed/abnormal ossification of bones of the hands and feet, joint contractures, and dysmorphic facial features may accompany. A single recurrent mutation (c. Read More

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http://dx.doi.org/10.1002/ajmg.a.60686DOI Listing
December 2018

A framework for understanding quality of life domains in individuals with the CDKL5 deficiency disorder.

Am J Med Genet A 2018 Dec 18. Epub 2018 Dec 18.

Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.

The CDKL5 deficiency disorder (CDD) is a rare condition caused by spontaneous mutations on the cyclin-dependent kinase-like 5 (CDKL5) gene. It is a severe and complex disability that markedly affects the individual's health and wellbeing. This study aimed to identify the quality of life (QOL) domains important for individuals with CDD. Read More

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http://dx.doi.org/10.1002/ajmg.a.61012DOI Listing
December 2018

Newborn screening for Prader-Willi syndrome is feasible: Early diagnosis for better outcomes.

Am J Med Genet A 2018 Dec 17. Epub 2018 Dec 17.

Department of Pediatrics, Division of Genetics and Metabolism, University of California, Irvine, California.

Prader-Willi syndrome (PWS), is a complex genetic disease affecting 1/15,000 individuals, characterized by lack of expression of genes on the paternal chromosome 15q11-q13 region. Clinical features include central hypotonia, poor suck, learning and behavior problems, growth hormone deficiency with short stature, hyperphagia, and morbid obesity. Despite significant advances in genetic testing, the mean age for diagnosis in PWS continues to lag behind. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.60681
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http://dx.doi.org/10.1002/ajmg.a.60681DOI Listing
December 2018
1 Read

Hypermobility in individuals with Kabuki syndrome: The effect of growth hormone treatment.

Am J Med Genet A 2018 Dec 17. Epub 2018 Dec 17.

Department of Pediatrics, Maastricht University Medical Center+, Maastricht, The Netherlands.

Kabuki syndrome (KS) is a multiple congenital malformation syndrome which has been described across all ethnic groups. Most KS patients possess two genetic subtypes: KMT2D-associated, autosomal-dominant KS type 1 (KS1; OMIM 147920); and KDM6A-associated, X-linked-dominant KS type 2. Generalized joint hypermobility is one feature of KS, but its exact incidence and pattern is not well described in the literature. Read More

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http://dx.doi.org/10.1002/ajmg.a.60696DOI Listing
December 2018

A homozygous canonical splice acceptor site mutation in PRUNE1 is responsible for a rare childhood neurodegenerative disease in Manitoba Cree families.

Am J Med Genet A 2018 Dec 17. Epub 2018 Dec 17.

Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Autosomal recessive PRUNE1 mutations are reported to cause a severe neurodevelopmental disorder with microcephaly, hypotonia, and brain malformations. We describe clinical and neuropathological features in a cohort of nine individuals of Cree descent who, because of a founder effect, are homozygous for the same PRUNE1 mutation. They follow the course of a combined neuromuscular and neurodegenerative disease, rather than a pure failure of normal development. Read More

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http://dx.doi.org/10.1002/ajmg.a.60690DOI Listing
December 2018

Identification of pathogenic YY1AP1 splice variants in siblings with Grange syndrome by whole exome sequencing.

Am J Med Genet A 2018 Dec 17. Epub 2018 Dec 17.

Department of Human Genetics, University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.

Grange syndrome is an autosomal recessive condition characterized by arterial occlusions and hypertension. Syndactyly, brachydactyly, bone fragility, heart defects, and learning disabilities have also been reported. Loss-of-function variants in YY1AP1 have only recently been associated with Grange syndrome. Read More

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http://dx.doi.org/10.1002/ajmg.a.60700DOI Listing
December 2018

Will the real Moebius syndrome please stand up? A systematic review of the literature and statistical cluster analysis of clinical features.

Am J Med Genet A 2018 Dec 17. Epub 2018 Dec 17.

Facial Nerve Programme, Regional Paediatric Burns and Plastic Surgery Service, Alder Hey Children's Foundation Trust, Liverpool, United Kingdom.

Moebius syndrome is a highly variable syndrome with abducens and facial nerve palsy as core features. Strict diagnostic criteria do not exist and the inconsistency of the associated features makes determination difficult. To determine what features are associated with Moebius syndrome we performed a systematic literature review resulting in a composite case series of 449 individuals labeled with Moebius syndrome. Read More

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http://dx.doi.org/10.1002/ajmg.a.60683DOI Listing
December 2018

Clinical report follow up: Type 1 Collagenopathy presenting with a Russell-Silver phenotype.

Am J Med Genet A 2018 Dec 17. Epub 2018 Dec 17.

Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.

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http://dx.doi.org/10.1002/ajmg.a.60680DOI Listing
December 2018

Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant.

Am J Med Genet A 2018 Dec 17. Epub 2018 Dec 17.

Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.

Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Read More

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http://doi.wiley.com/10.1002/ajmg.a.60678
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http://dx.doi.org/10.1002/ajmg.a.60678DOI Listing
December 2018
5 Reads

A case of YY1-associated syndromic learning disability or Gabriele-de Vries syndrome with myasthenia gravis.

Am J Med Genet A 2018 Dec 14. Epub 2018 Dec 14.

Department of Neurology, Mayo Clinic, Mayo Clinic, Scottsdale, Arizona.

Exome sequencing is being used increasingly to evaluate patients with intellectual disability. YY1 is a ubiquitously distributed transcription factor belonging to the GLIKruppel class of zinc finger proteins recently recognized as the causative gene in 23 patients for the Gabriele-de Vries syndrome. We report a new case with similar features and a novel variant in YY1, in a region of the gene, which has not previously been reported. Read More

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http://dx.doi.org/10.1002/ajmg.a.40626DOI Listing
December 2018
1 Read

A homozygous MITF mutation leads to familial Waardenburg syndrome type 4.

Am J Med Genet A 2018 Dec 14. Epub 2018 Dec 14.

Department of Otolaryngology - Head and Neck Surgery, The Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Waardenburg syndrome (WS) is a genetic disorder characterized by hearing loss and pigmentary abnormalities with variable penetrance. Though heterozygous mutations in MITF are a major cause for Waardenburg syndrome type 2 (WS2), homozygous mutations in this gene and the associated phenotype have been rarely characterized. In this study, we identified a novel p. Read More

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http://dx.doi.org/10.1002/ajmg.a.60693DOI Listing
December 2018
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GPR126: A novel candidate gene implicated in autosomal recessive intellectual disability.

Am J Med Genet A 2018 Dec 14. Epub 2018 Dec 14.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Intellectual disability (ID), a genetically and clinically heterogeneous disorder, affects 1%-3% of the general population and is a major health problem, especially in developing countries and in populations with a high frequency of consanguineous marriage. Using whole exome sequencing, a homozygous missense variation (c.3264G>C, p. Read More

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http://dx.doi.org/10.1002/ajmg.a.40531DOI Listing
December 2018

An N-terminal heterozygous missense CASK mutation is associated with microcephaly and bilateral retinal dystrophy plus optic nerve atrophy.

Am J Med Genet A 2018 Dec 14. Epub 2018 Dec 14.

Virginia Tech Carilion Research Institute, Roanoke, Virginia.

Heterozygous loss-of-function mutations in the X-linked gene CASK are associated with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) and ophthalmological disorders including optic nerve atrophy (ONA) and optic nerve hypoplasia (ONH). Recently, we have demonstrated that CASK mice display ONH with 100% penetrance but exhibit no change in retinal lamination or structure. It is not clear if CASK loss-of-function predominantly affects retinal ganglion cells, or if other retinal cells like photoreceptors are also involved. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.60687
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http://dx.doi.org/10.1002/ajmg.a.60687DOI Listing
December 2018
2 Reads

A novel autosomal dominant mutation in SOX18 resulting in a fatal case of hypotrichosis-lymphedema-telangiectasia syndrome.

Am J Med Genet A 2018 Dec 14. Epub 2018 Dec 14.

Department of Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, California.

Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is a rare disorder caused by autosomal recessive and autosomal dominant mutations in SOX18. This gene encodes a transcription factor involved in the regulation and development of the human vasculature, lymphatic, and integumentary systems. Individuals with HLTS develop varying degrees of hypotrichosis, lymphedema, and telangiectasias. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.40532
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http://dx.doi.org/10.1002/ajmg.a.40532DOI Listing
December 2018
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High risk of spontaneous preterm birth among infants with gastroschisis.

Am J Med Genet A 2018 Dec 14. Epub 2018 Dec 14.

California Preterm Birth Initiative, University of California San Francisco, San Francisco, California.

We examined the association between gastroschisis and preterm birth (PTB, <37 weeks) by subtype. The sample was drawn from singleton live births in California from 2007 to 2012 contained in a birth cohort file maintained by the California Office of Statewide Health Planning and Development (n = 2,891,965; 1,421 with gastroschisis). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for PTB by gestational age (<34, 34-36, and any <37 weeks) and by type (spontaneous labor with intact membranes, preterm premature rupture of the membranes [PPROM], provider initiated) and were adjusted for maternal characteristics. Read More

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http://dx.doi.org/10.1002/ajmg.a.60675DOI Listing
December 2018

The progression of Wiedemann-Steiner syndrome in adulthood and two novel variants in the KMT2A gene.

Am J Med Genet A 2018 Dec 14. Epub 2018 Dec 14.

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.

Wiedemann-Steiner syndrome is a genetic condition associated with dysmorphic facies, hypertrichosis, short stature, developmental delay, and intellectual disability. Congenital malformations of the cerebral, cardiac, renal, and optic structures have also been reported. Because the majority of reported individuals with this condition have been under age 20, the long-term prognosis is not well defined. Read More

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http://dx.doi.org/10.1002/ajmg.a.60698DOI Listing
December 2018

COMMENTARY-The Saul-Wilson syndrome from its early days until now.

Am J Med Genet A 2018 Dec 13. Epub 2018 Dec 13.

Department of Pediatrics, University of Virginia School of Medicine, University of Virginia, Charlottesville, Virginia.

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http://dx.doi.org/10.1002/ajmg.a.8DOI Listing
December 2018

Associated anomalies in cases with anorectal anomalies.

Am J Med Genet A 2018 Dec 12:e40530. Epub 2018 Dec 12.

Laboratoire de Génétique Médicale, Faculté de Médecine, Université de Strasbourg, Strasbourg cedex, France.

Anorectal anomalies (ARA) are common congenital anomalies. The etiology of ARA is unclear and its pathogenesis is controversial. Cases with ARA often have other non-ARA-associated congenital anomalies. Read More

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http://dx.doi.org/10.1002/ajmg.a.40530DOI Listing
December 2018

A biallelic truncating AEBP1 variant causes connective tissue disorder in two siblings.

Am J Med Genet A 2018 Dec 11. Epub 2018 Dec 11.

Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Biallelic variants in the AEBP1 gene cause a novel autosomal-recessive connective tissue disorder (CTD) reminiscent of Ehlers-Danlos Syndrome (EDS). The four previously reported individuals show considerable clinical variability. Unbiased high-throughput sequencing enables the rapid identification of additional cases for such rare entities. Read More

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http://dx.doi.org/10.1002/ajmg.a.60679DOI Listing
December 2018

Novel variants in SPTAN1 without epilepsy: An expansion of the phenotype.

Am J Med Genet A 2018 Dec 11. Epub 2018 Dec 11.

Office of the Clinical Director, NHGRI, and NIH Undiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, Maryland.

We describe two unrelated children with de novo variants in the non-erythrocytic alpha-II-spectrin (SPTAN1) gene who have hypoplastic brain structures, intellectual disability, and both fine and gross motor impairments. Using agnostic exome sequencing, we identified a nonsense variant creating a premature stop codon in exon 21 of SPTAN1, and in a second patient we identified an intronic substitution in SPTAN1 prior to exon 50 creating a new donor acceptor site. Neither of these variants has been described previously. Read More

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http://dx.doi.org/10.1002/ajmg.a.40628DOI Listing
December 2018

The oculoauriculofrontonasal syndrome: Further clinical characterization and additional evidence suggesting a nontraditional mode of inheritance.

Am J Med Genet A 2018 Dec 10. Epub 2018 Dec 10.

Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est, Centre Hospitalier Universitaire Dijon, Dijon, France.

The oculoauriculofrontonasal syndrome (OAFNS) is a rare disorder characterized by the association of frontonasal dysplasia (widely spaced eyes, facial cleft, and nose abnormalities) and oculo-auriculo-vertebral spectrum (OAVS)-associated features, such as preauricular ear tags, ear dysplasia, mandibular asymmetry, epibulbar dermoids, eyelid coloboma, and costovertebral anomalies. The etiology is unknown so far. This work aimed to identify molecular bases for the OAFNS. Read More

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http://dx.doi.org/10.1002/ajmg.a.40662DOI Listing
December 2018

Malan syndrome: Extension of genotype and phenotype spectrum.

Am J Med Genet A 2018 Dec 10. Epub 2018 Dec 10.

Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Malan syndrome and Marshall-Smith syndrome (MSS) are allelic disorders caused by mutation in NFIX gene. We report a 3-year- 6 months- old female with clinical features suggestive of Malan syndrome with mutation in exon 2 of NFIX gene. NFIX gene, where most of the mutations in Malan syndrome are located. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.40663
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http://dx.doi.org/10.1002/ajmg.a.40663DOI Listing
December 2018
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Genotype and phenotype correlations for SHANK3 de novo mutations in neurodevelopmental disorders.

Am J Med Genet A 2018 Dec 9. Epub 2018 Dec 9.

Center for Medical Genetics & Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

SHANK3 has been identified as the causative gene of 22q13.3 microdeletion syndrome phenotype. De novo mutations (DNMs) of SHANK3 were subsequently identified in patients with several neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia (SCZ), a Rett syndrome-like phenotype, and intellectual disability (ID). Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.40666
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http://dx.doi.org/10.1002/ajmg.a.40666DOI Listing
December 2018
3 Reads

Single suture craniosynostosis: Identification of rare variants in genes associated with syndromic forms. Am J Med Genet A. 2018 Feb;176(2):290-300.

Am J Med Genet A 2018 Nov 20;176(11):2522. Epub 2018 Sep 20.

Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington.

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http://dx.doi.org/10.1002/ajmg.a.38846DOI Listing
November 2018

In This Issue.

Authors:

Am J Med Genet A 2018 Nov;176(11):2236

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http://dx.doi.org/10.1002/ajmg.a.60673DOI Listing
November 2018

Expanding clinical phenotype in CACNA1C related disorders: From neonatal onset severe epileptic encephalopathy to late-onset epilepsy.

Am J Med Genet A 2018 Dec 4. Epub 2018 Dec 4.

Division of Pediatric Neurology, Department of Neurology, University of Washington, Seattle, Washington.

CACNA1C (NM_000719.6) encodes an L-type calcium voltage-gated calcium channel (Ca 1.2), and pathogenic variants have been associated with two distinct clinical entities: Timothy syndrome and Brugada syndrome. Read More

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http://dx.doi.org/10.1002/ajmg.a.40657DOI Listing
December 2018
2 Reads

Features of multiple self-healing squamous epithelioma and Loeys-Dietz syndrome in a patient with a novel TGFBR1 variant.

Am J Med Genet A 2018 Dec 4. Epub 2018 Dec 4.

Genetic Health Service, Wellington, New Zealand.

Multiple self-healing squamous epithelioma (MSSE, Ferguson-Smith disease) and Loeys-Dietz syndrome (LDS) are allelic conditions associated with pathogenic variants in the transforming growth factor beta receptor 1 gene (TGFBR1). We describe a patient with a novel missense variant in this gene: c.664G > A, p. Read More

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http://doi.wiley.com/10.1002/ajmg.a.40652
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http://dx.doi.org/10.1002/ajmg.a.40652DOI Listing
December 2018
4 Reads

Novel truncating mutation in TENM3 in siblings with motor developmental delay, ocular coloboma, oval cornea, without microphthalmia.

Am J Med Genet A 2018 Dec 4. Epub 2018 Dec 4.

Section of Human Biochemical Genetics, 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.40658DOI Listing
December 2018

Combined CNV, haplotyping and whole exome sequencing enable identification of two distinct novel EYS mutations causing RP in a single inbred tribe.

Am J Med Genet A 2018 Dec 4. Epub 2018 Dec 4.

The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Whole exome sequencing (WES) has become routine in clinical practice, especially in studies of recessive hereditary diseases in inbred consanguineous families, where homozygosity of a founder mutation is assumed. Multiple members of two consanguineous families of a single Bedouin tribe were diagnosed with apparently autosomal recessive/pseudo-dominant retinitis pigmentosa (RP). Affected individuals exhibited severe visual impairment with nyctalopia, marked constriction of visual fields, markedly reduced and delayed responses on electro-retinography (ERG) and eventual loss of central vision. Read More

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http://doi.wiley.com/10.1002/ajmg.a.40668
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http://dx.doi.org/10.1002/ajmg.a.40668DOI Listing
December 2018
4 Reads

Prenatal and postnatal presentation of PRMT7 related syndrome: Expanding the phenotypic manifestations.

Am J Med Genet A 2018 Dec 4. Epub 2018 Dec 4.

Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel.

Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyze the transfer of methyl groups from S-adenosyl-l-methionine to nitrogen atoms on arginine residues. Arginine methylation is involved in multiple biological processes, such as signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. Currently, 10 patients have been described with mutations in PRMT7. Read More

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http://dx.doi.org/10.1002/ajmg.a.6DOI Listing
December 2018
2 Reads

The accuracy of computer-based diagnostic tools for the identification of concurrent genetic disorders.

Am J Med Genet A 2018 Nov 26. Epub 2018 Nov 26.

Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio.

The increasing use of next-generation sequencing, especially clinical exome sequencing, has revealed that individuals having two coexisting genetic conditions are not uncommon occurrences. This pilot study evaluates the efficacy of two methodologically distinct computational differential diagnosis generating tools-FindZebra and SimulConsult-in identifying multiple genetic conditions in a single patient. Clinical query terms were generated for each of 15 monogenic disorders that were effective in resulting in the top 10 list of differential diagnoses for each of the 15 monogenic conditions when entered into these bioinformatics tools. Read More

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http://dx.doi.org/10.1002/ajmg.a.40651DOI Listing
November 2018
2.159 Impact Factor

Gain-of-function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities.

Am J Med Genet A 2018 Nov 26. Epub 2018 Nov 26.

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

Polyamines serve a number of vital functions in humans, including regulation of cellular proliferation, intracellular signaling, and modulation of ion channels. Ornithine decarboxylase 1 (ODC1) is the rate-limiting enzyme in endogenous polyamine synthesis. In this report, we present four patients with a distinct neurometabolic disorder associated with de novo heterozygous, gain-of-function variants in the ODC1 gene. Read More

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http://doi.wiley.com/10.1002/ajmg.a.60677
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http://dx.doi.org/10.1002/ajmg.a.60677DOI Listing
November 2018
3 Reads

First reported adult patient with TARP syndrome: A case report.

Am J Med Genet A 2018 Nov 21. Epub 2018 Nov 21.

Research and Knowledge Center in Sensory Genetics, Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark.

TARP syndrome (talipes equinovarus, atrial septal defect, Robin sequence, and persistence of the left superior vena cava) is a rare X-linked syndrome often resulting in pre- or post-natal lethality in affected males. In 2010, RBM10 was identified as the disease-causing gene, and we describe the first adult patient with TARP syndrome at age 28 years, hereby expanding the phenotypic spectrum. Our patient had Robin sequence, atrial septal defect, intellectual disability, scoliosis, and other findings previously associated with TARP syndrome. Read More

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http://dx.doi.org/10.1002/ajmg.a.40638DOI Listing
November 2018
14 Reads

Japanese patient with Cole-carpenter syndrome with compound heterozygous variants of SEC24D.

Am J Med Genet A 2018 Nov 21. Epub 2018 Nov 21.

Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.

Cole-Carpenter syndrome is a rare skeletal dysplasia associated with low-bone mass or an osteogenesis imperfecta (OI)-like syndrome. Only 3 and 6 variants in SEC24D have been reported in patients with Cole-Carpenter syndrome type 2 and autosomal recessive OI, respectively. We describe a 15-year-old Japanese boy with short stature of the short-trunk type and craniofacial abnormalities including ocular proptosis, marked frontal bossing, midface hypoplasia, and micrognathia. Read More

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http://dx.doi.org/10.1002/ajmg.a.40643DOI Listing
November 2018
1 Read

Unmasking familial CPX by WES and identification of novel clinical signs.

Am J Med Genet A 2018 Nov 21:e40630. Epub 2018 Nov 21.

Human Molecular Genetics, de Duve Institute, University of Louvain, Brussels, Belgium.

Mutations in the T-Box transcription factor gene TBX22 are found in X-linked Cleft Palate with or without Ankyloglossia syndrome (CPX syndrome). In addition to X-linked inheritance, ankyloglossia, present in the majority of CPX patients, is an important diagnostic marker, but it is frequently missed or unreported, as it is a "minor" feature. Other described anomalies include cleft lip, micro and/or hypodontia, and features of CHARGE syndrome. Read More

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http://dx.doi.org/10.1002/ajmg.a.40630DOI Listing
November 2018
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Atypical presentation of pediatric BRAF RASopathy with acute encephalopathy.

Am J Med Genet A 2018 Nov 21:e40635. Epub 2018 Nov 21.

Laboratorio di Genetica Medica, ASST Papa Giovanni XXIII, Bergamo, Italy.

We report a 9-year-old girl with hypotonia, severe motor delay, absent speech, and facial dysmorphism who developed acute encephalopathy with severe neurological outcome. Trio-based whole exome sequencing (WES) analysis detected a de novo heterozygous mutation in the BRAF gene leading to the diagnosis of an atypical presentation of cardiofaciocutaneous (CFC) syndrome. This is the second case of CFC syndrome complicated with acute encephalopathy reported in the literature and supports the hypothesis that acute encephalopathy might be one of the complications of the syndrome due to an intrinsic susceptibility to this acute event. Read More

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http://dx.doi.org/10.1002/ajmg.a.40635DOI Listing
November 2018

Autosomal recessive Stickler syndrome resulting from a COL9A3 mutation.

Am J Med Genet A 2018 Nov 18. Epub 2018 Nov 18.

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

Stickler syndrome is a connective tissue disorder characterized by hearing loss, ocular anomalies, palatal defects, and skeletal abnormalities. The autosomal dominant form is the most common, but autosomal recessive forms have also been described. We report the second case of autosomal recessive Stickler syndrome due to homozygosity for a loss of function mutation in COL9A3, which encodes the α3 chain of type IX procollagen. Read More

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http://doi.wiley.com/10.1002/ajmg.a.40647
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http://dx.doi.org/10.1002/ajmg.a.40647DOI Listing
November 2018
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Microphthalmia is not a mandatory finding in X-linked recessive syndromic microphthalmia caused by the recurrent BCOR variant p.Pro85Leu.

Am J Med Genet A 2018 Nov 18. Epub 2018 Nov 18.

Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Mutations in BCOR cause X-linked dominant and X-linked recessive forms of syndromic microphthalmia. By exome sequencing, we identified the recurrent BCOR mutation p.Pro85Leu in two brothers and their unaffected mother. Read More

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http://doi.wiley.com/10.1002/ajmg.a.40640
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http://dx.doi.org/10.1002/ajmg.a.40640DOI Listing
November 2018
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Infant male with TARP syndrome: Review of clinical features, prognosis, and commonalities with previously reported patients.

Am J Med Genet A 2018 Nov 18. Epub 2018 Nov 18.

Division of Neonatal Medicine, Mayo Clinic, Rochester, Minnesota.

TARP syndrome (talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava) is a rare X-linked condition. As more patients are identified through genetic testing, it is increasingly clear that the original TARP acronym does not fully describe the complete phenotypic spectrum of this syndrome. The presented patient had genetically confirmed TARP syndrome and demonstrated new findings of hydronephrosis and hemodynamically significant hypertrophic obstructive cardiomyopathy. Read More

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http://doi.wiley.com/10.1002/ajmg.a.40645
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http://dx.doi.org/10.1002/ajmg.a.40645DOI Listing
November 2018
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Extension of the mutational and clinical spectrum of SOX2 related disorders: Description of six new cases and a novel association with suprasellar teratoma.

Am J Med Genet A 2018 Nov 18. Epub 2018 Nov 18.

Department of Genetics, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.

SOX2 is a transcription factor that is essential for maintenance of pluripotency and has several conserved roles in early embryonic development. Heterozygous loss-of-function variants in SOX2 are identified in approximately 40% of all cases of bilateral anophthalmia/micropthalmia (A/M). Increasingly SOX2 mutation-positive patients without major eye findings, but with a range of other developmental disorders including autism, mild to moderate intellectual disability with or without structural brain changes, esophageal atresia, urogenital anomalies, and endocrinopathy are being reported, suggesting that the clinical phenotype associated with SOX2 loss is much broader than previously appreciated. Read More

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http://doi.wiley.com/10.1002/ajmg.a.40644
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http://dx.doi.org/10.1002/ajmg.a.40644DOI Listing
November 2018
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An additional case of Hennekam lymphangiectasia-lymphedema syndrome caused by loss-of-function mutation in ADAMTS3.

Am J Med Genet A 2018 Nov 18. Epub 2018 Nov 18.

Ambry Genetics, Aliso Viejo, California, USA.

Hennekam lymphangiectasia-lymphedema syndrome (HKLLS) is a genetically heterogeneous lymphatic dysplasia with characteristic of facial dysmorphism, neurocognitive impairments, and abnormalities of the pericardium, intestinal tract, and extremities. It is an autosomal recessive condition caused by biallelic mutations in CCBE1 (collagen- and calcium-binding epidermal growth factor domain-containing protein 1) (HKLLS1; OMIM 235510) or FAT4 (HKLLS2; OMIM 616006). CCBE1 acts via ADAMTS3 (a disintegrin and metalloprotease with thrombospondin motifs-3 protease) to enhance vascular endothelial growth factor C signaling. Read More

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http://doi.wiley.com/10.1002/ajmg.a.40633
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http://dx.doi.org/10.1002/ajmg.a.40633DOI Listing
November 2018
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Next generation sequencing-based molecular diagnosis in familial congenital cataract expands the mutational spectrum in known congenital cataract genes.

Am J Med Genet A 2018 Nov 18. Epub 2018 Nov 18.

Research Unit, Genetics Department, Institute of Ophthalmology, "Conde de Valenciana", Mexico City, Mexico.

Congenital cataract (CC) is a significant cause of childhood blindness worldwide. CC is a genetically heterogeneous disease because mutations in over 40 genes have been demonstrated to cause the disorder and up to 40% of cases arise from single-gene mutations. Hence, next generation sequencing (NGS) of deoxyribonucleic acid is a suitable approach for CC molecular diagnosis. Read More

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http://doi.wiley.com/10.1002/ajmg.a.40524
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http://dx.doi.org/10.1002/ajmg.a.40524DOI Listing
November 2018
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Ablepharon and craniosynostosis in a patient with a localized TWIST1 basic domain substitution.

Am J Med Genet A 2018 Nov 18. Epub 2018 Nov 18.

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

The TWIST family is a group of highly conserved basic helix-loop-helix transcription factors. In humans, TWIST1 haploinsufficiency causes Saethre-Chotzen syndrome, which is characterized by craniosynostosis. Heterozygous localized TWIST1 and TWIST2 basic domain substitutions exert antimorphic effects to cause Sweeney-Cox syndrome, Barber-Say syndrome, and ablepharon-macrostomia syndrome, respectively. Read More

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http://doi.wiley.com/10.1002/ajmg.a.40525
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http://dx.doi.org/10.1002/ajmg.a.40525DOI Listing
November 2018
4 Reads