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    7894 results match your criteria American Journal of Medical Genetics Part A[Journal]

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    Cover Image, Volume 173A, Number 10, October 2017.
    Am J Med Genet A 2017 Oct;173(10)
    Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
    The cover image, by Rani A. Bashir et al., is based on the Original Article Lin-Gettig syndrome: Craniosynostosis expands the spectrum of the KAT6B related disorders, DOI: 10. Read More

    De novo SETD5 loss-of-function variant as a cause for intellectual disability in a 10-year old boy with an aberrant blind ending bronchus.
    Am J Med Genet A 2017 Sep 14. Epub 2017 Sep 14.
    Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
    Although rare, 3p microdeletion cases have been well described in the clinical literature. The clinical phenotype includes; intellectual disability (ID), growth retardation, facial dysmorphism, and cardiac malformations. Advances in chromosome microarray (CMA) testing narrowed the 3p25 critical region to a 124 kb region, and recent Whole Exome Sequencing (WES) studies have suggested that the SETD5 gene contributes significantly to the 3p25 phenotype. Read More

    HLX is a candidate gene for a pattern of anomalies associated with congenital diaphragmatic hernia, short bowel, and asplenia.
    Am J Med Genet A 2017 Sep 12. Epub 2017 Sep 12.
    Molecular Genetics of Development Laboratory, Department of Biological Sciences and BioMed Research Center, Faculty of Sciences, University of Quebec at Montreal, Montreal, Quebec.
    Isolated congenital diaphragmatic hernia is often a sporadic event with a low recurrence risk. However, underlying genetic etiologies, such as chromosome anomalies or single gene disorders, are identified in a small number of individuals. We describe two fetuses with a unique pattern of multiple congenital anomalies, including diaphragmatic hernia, short bowel and asplenia, born to first-cousin parents. Read More

    Compound heterozygous TRPV4 mutations in two siblings with a complex phenotype including severe intellectual disability and neuropathy.
    Am J Med Genet A 2017 Sep 12. Epub 2017 Sep 12.
    Department of Pediatrics, Division of Biochemical Diseases, University of British Columbia, Vancouver, Canada.
    TRPV4 encodes a polymodal calcium-permeable plasma membrane channel. Dominant pathogenic mutations in TRPV4 lead to a wide spectrum of abnormal phenotypes. This is the first report of biallelic TRPV4 mutations and we describe two compound heterozygous siblings presenting with a complex phenotype including severe neuromuscular involvement. Read More

    Treating pediatric neuromuscular disorders: The future is now.
    Am J Med Genet A 2017 Sep 10. Epub 2017 Sep 10.
    Department of Pediatrics, Clinical Neurological Sciences, Epidemiology, Western University, London, Ontario, Canada.
    Pediatric neuromuscular diseases encompass all disorders with onset in childhood and where the primary area of pathology is in the peripheral nervous system. These conditions are largely genetic in etiology, and only those with a genetic underpinning will be presented in this review. This includes disorders of the anterior horn cell (e. Read More

    Intrafamilial variability of the triphalangeal thumb phenotype in a Dutch population: Evidence for phenotypic progression over generations?
    Am J Med Genet A 2017 Sep 10. Epub 2017 Sep 10.
    Department of Plastic and Reconstructive Surgery and Hand Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
    Triphalangeal thumbs (TPTs) are regularly caused by mutations in the ZRS in LMBR1. Phenotypic variability can be present in TPT-families. However, recent observations suggest an increased occurrence of severe phenotypes in the Dutch TPT-population. Read More

    Pharmacological interventions to improve cognition and adaptive functioning in Down syndrome: Strides to date.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
    Although an increasing number of clinical trials have been developed for cognition in Down syndrome, there has been limited success to date in identifying effective interventions. This review describes the progression from pre-clinical studies with mouse models to human clinical trials research using pharmacological interventions to improve cognition and adaptive functioning in Down syndrome. We also provide considerations for investigators when conducting human clinical trials and describe strategies for the pharmaceutical industry to advance the field in drug discovery for Down syndrome. Read More

    Testing the face shape hypothesis in twins discordant for nonsyndromic orofacial clefting.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
    Nonsyndromic orofacial clefts (OFCs) are complex traits characterized by multifactorial inheritance and wide phenotypic variability. Numerous studies have shown subtle differences in the faces of unaffected relatives from cleft families compared to controls, the implication being that such outward differences are an incomplete expression reflecting an underlying genetic predisposition. Twins discordant for OFCs provide a unique opportunity to further test this idea, as the unaffected co-twin shares on average 50% (for dizygotic twins) and 100% (for monozygotic twins) of the genetic risk factors as the affected twin. Read More

    Genotypic-phenotypic features and enzyme replacement therapy outcome in patients with mucopolysaccharidosis VI from Turkey.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Hacettepe University Children Hospital, Division of Metabolism, Ankara, Turkey.
    Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD) characterized by a chronic, progressive course with multiorgan involvement. In our study, clinical, biochemical, molecular findings, and response to enzyme replacement therapy (ERT) for at least 6 months were evaluated in 20 patients with MPS VI. Treatment effects on clinical findings such as liver and spleen sizes, cardiac and respiratory parameters, visual and auditory changes, joints' range of motions, endurance tests and changes in urinary glycosaminoglycan excretions, before and after ERT were analyzed. Read More

    Confirmation of an ARID2 defect in SWI/SNF-related intellectual disability.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
    We present a 4-year-old girl with delayed neuromotor development, short stature of prenatal onset, and specific behavioral and craniofacial features harboring an intragenic deletion in the ARID2 gene. The phenotype confirmed the major features of the recently described ARID2-related intellectual disability syndrome. However, our patient showed overlapping features with Nicolaides-Baraitser syndrome and Coffin-Siris syndrome, providing further arguments to reclassify these disorders as "SWI/SNF-related intellectual disability syndromes. Read More

    Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
    Noonan syndrome (NS) is an autosomal dominant multisystem condition with a variable phenotype. The most characteristic features are short stature, congenital heart defects, and recognizable facial features. Mutations in SOS1 are found in 10-20% of patients with NS. Read More

    Peeling skin syndrome associated with novel variant in FLG2 gene.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    King Abdullah International Medical Research Centre, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
    Peeling skin syndrome is a rare genodermatosis characterized by variably pruritic superficial generalized peeling of the skin with several genes involved until now little is known about the association between FLG2 and peeling skin syndrome. We describe multiple family members from a consanguineous Saudi family with peeling skin syndrome. Next Generation Sequencing identifies a cosegregating novel variant in FLG2 c. Read More

    Two novel mutations in XYLT2 cause spondyloocular syndrome.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    We report on two new patients with spondyloocular syndrome. Both patients harbor novel homozygous mutations in the XYLT2 gene. The patients present severe generalized osteoporosis, multiple fractures, short stature, cataract, and mild hearing impairment. Read More

    Congenital heart defects in molecularly proven Kabuki syndrome patients.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Medical Genetics Unit, Medical Genetics Laboratory, Pediatric Cardiology, Bambino Gesù Pediatric Hospital, IRCCS, Rome, Italy.
    The prevalence of congenital heart defects (CHD) in Kabuki syndrome ranges from 28% to 80%. Between January 2012 and December 2015, 28 patients had a molecularly proven diagnosis of Kabuki syndrome. Pathogenic variants in KMT2D (MLL2) were detected in 27 patients, and in KDM6A gene in one. Read More

    Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Mutations in GLE1 underlie Lethal Congenital Contracture syndrome (LCCS) and Lethal Arthrogryposis with Anterior Horn Cell Disease (LAAHD). Both LCCS and LAAHD are characterized by reduced fetal movements, congenital contractures, and a severe form of motor neuron disease that results in fetal death or death in the perinatal period, respectively. We identified bi-allelic mutations in GLE1 in two unrelated individuals with motor delays, feeding difficulties, and respiratory insufficiency who survived beyond the perinatal period. Read More

    Chimerism for 20q11.2 microdeletion of GDF5 explains discordant phenotypes in monochorionic-diamniotic twins.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Division of Molecular Pathology and Genomics, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota.
    Microdeletions of 20q11.2 are rare but have been associated with characteristic clinical findings. A 1. Read More

    Novel homozygous missense mutation in NT5C2 underlying hereditary spastic paraplegia SPG45.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London, London, UK.
    SPG45 is a rare form of autosomal recessive spastic paraplegia associated with mental retardation. Detailed phenotyping and mutation analysis was undertaken in three individuals with SPG45 from a consanguineous family of Arab Muslim origin. Using whole-exome sequencing, we identified a novel homozygous missense mutation in NT5C2 (c. Read More

    FOXP1 haploinsufficiency: Phenotypes beyond behavior and intellectual disability?
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Department of Pediatrics, University of South Dakota and Sanford Health, Sioux Falls, South Dakota.
    The forkhead box (FOX) transcription factors have roles in development, carcinogenesis, metabolism, and immunity. In humans FOXP1 mutations have been associated with language and speech defects, intellectual disability, autism spectrum disorder, facial dysmorphisms, and congenital anomalies of the kidney and urinary tract. In mice, Foxp1 plays critical roles in development of the spinal motor neurons, lymphocytes, cardiomyocytes, foregut, and skeleton. Read More

    A novel missense variant in the GLI3 zinc finger domain in a family with digital anomalies.
    Am J Med Genet A 2017 Sep 8. Epub 2017 Sep 8.
    Division of Medical Genetics, Stanford University School of Medicine, Stanford, California.
    Mutations in GLI3, which encodes a transcription factor of the Hedgehog signaling pathway, cause several developmental anomalies linked to inappropriate tissue patterning. Here, we report a novel missense variant in the fifth zinc finger domain of GLI3 (c.1826G>A; p. Read More

    Challenges in measuring the effects of pharmacological interventions on cognitive and adaptive functioning in individuals with Down syndrome: A systematic review.
    Am J Med Genet A 2017 Aug 31. Epub 2017 Aug 31.
    Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
    We systematically reviewed the measures used in pharmaceutical trials in children/adults with Down syndrome without dementia. Our purpose was to identify developmentally appropriate outcome measures capable of detecting changes in cognitive and adaptive functioning in this population. Eleven studies were included and used diverse outcome measures across the domains of language, memory, attention, behavior, and executive/adaptive functioning. Read More

    Factors related to home health-care transition in trisomy 13.
    Am J Med Genet A 2017 Oct 29;173(10):2635-2640. Epub 2017 Aug 29.
    Division of Neonatology, Center for Maternal-Neonatal Care Nagoya University Hospital, Nagoya, Japan.
    Trisomy 13 (T13) is accompanied by severe complications, and it can be challenging to achieve long-term survival without aggressive treatment. However, recently, some patients with T13 have been receiving home care. We conducted this study to investigate factors related to home health-care transition for patients with T13. Read More

    Encephalopathy caused by novel mutations in the CMP-sialic acid transporter, SLC35A1.
    Am J Med Genet A 2017 Aug 29. Epub 2017 Aug 29.
    Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
    Transport of activated nucleotide-sugars into the Golgi is critical for proper glycosylation and mutations in these transporters cause a group of rare genetic disorders termed congenital disorders of glycosylation. We performed exome sequencing on an individual with a profound neurological presentation and identified rare compound heterozygous mutations, p.Thr156Arg and p. Read More

    Congenital neurodevelopmental anomalies in pediatric and young adult cancer.
    Am J Med Genet A 2017 Oct 29;173(10):2670-2679. Epub 2017 Aug 29.
    Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, Saint Louis, Missouri.
    Congenital anomalies that are diagnosed in at least 120,000 US infants every year are the leading cause of infant death and contribute to disability and pediatric hospitalizations. Several large-scale epidemiologic studies have provided substantial evidence of an association between congenital anomalies and cancer risk in children, suggesting potential underlying cancer-predisposing conditions and the involvement of developmental genetic pathways. Electronic medical records from 1,107 pediatric, adolescent, and young adult oncology patients were reviewed. Read More

    De novo pathogenic variant in TUBB2A presenting with arthrogryposis multiplex congenita, brain abnormalities, and severe developmental delay.
    Am J Med Genet A 2017 Oct 25;173(10):2725-2730. Epub 2017 Aug 25.
    Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
    Disorders of brain formation can occur from pathogenic variants in various alpha and beta tubulin genes. Heterozygous pathogenic variants in the beta tubulin isotype A gene, TUBB2A, have been recently implicated in brain malformations, seizures, and developmental delay. Limited information is known regarding the phenotypic spectrum associated with pathogenic variants in this gene given the rarity of the condition. Read More

    Prenatal presentation of Mabry syndrome with congenital diaphragmatic hernia and phenotypic overlap with Fryns syndrome.
    Am J Med Genet A 2017 Oct 17;173(10):2776-2781. Epub 2017 Aug 17.
    Drexel University College of Medicine, Philadelphia, Pennsylvania.
    We report on a family in which initial features were compatible with Fryns syndrome. The first sibling was a stillborn female with a left diaphragmatic hernia (DH). Her clinical features overlapped with Fryns syndrome. Read More

    Stakeholders in psychiatry and their attitudes toward receiving pertinent and incident findings in genomic research.
    Am J Med Genet A 2017 Oct 17;173(10):2649-2658. Epub 2017 Aug 17.
    Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
    Increasingly more psychiatric research studies use whole genome sequencing or whole exome sequencing. Consequently, researchers face difficult questions, such as which genomic findings to return to research participants and how. This study aims to gain more knowledge on the attitudes among potential research participants and health professionals toward receiving pertinent and incidental findings. Read More

    A new CUL4B variant associated with a mild phenotype and an exceptional pattern of leukoencephalopathy.
    Am J Med Genet A 2017 Oct 17;173(10):2803-2807. Epub 2017 Aug 17.
    Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany.
    Cabezas type of X-linked syndromic intellectual disability (MRXSC; MIM300354) is a rare X-linked recessive intellectual disability characterized primarily by intellectual disability, short stature, hypogonadism, and gait abnormalities. It is caused by a wide spectrum of hemizygous variants in CUL4B. In a 10-year-old boy with an exceptional leukoencephalopathy pattern, we identified a new missense variant p. Read More


    Dolichol kinase deficiency (DOLK-CDG): Two new cases and expansion of phenotype.
    Am J Med Genet A 2017 Sep;173(9):2428-2434
    Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska.
    Congenital disorders of glycosylation (CDGs) are a group of genetic diseases caused by mutations in genes that are necessary for the addition of oligosaccharides to acceptor proteins or lipids. An early step in this process requires dolichol kinase (DK) to catalyze the formation of dolichyl phosphate, which acts as a membrane anchor for initial attachment of sugar residues that are subsequently built up to oligosaccharides and transferred to acceptor proteins and lipids for further processing. Biallelic mutations in DOLK, the gene for DK, result in human in a CDG with variable symptoms, ranging from nonsyndromic dilated cardiomypopathy to severe multiorgan involvement. Read More


    Estimation of live birth and population prevalence of Down syndrome in nine U.S. states.
    Am J Med Genet A 2017 Oct 16;173(10):2710-2719. Epub 2017 Aug 16.
    Down Syndrome Program, Division of Medical Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.
    For all of the U.S. states with sufficient data, we estimated live birth and population prevalences for Down syndrome (DS). Read More

    Prevalence of gastrointestinal symptoms in Angelman syndrome.
    Am J Med Genet A 2017 Oct 16;173(10):2703-2709. Epub 2017 Aug 16.
    Department of Neurology, Angelman Syndrome Clinic, Massachusetts General Hospital, Boston, Massachusetts.
    Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, expressive speech impairment, movement disorder, epilepsy, and a happy demeanor. Children with AS are frequently reported to be poor feeders during infancy and as having gastrointestinal issues such as constipation, reflux, and abnormal food related behaviors throughout their lifetime. To assess the prevalence of gastrointestinal disorders in individuals with AS, we retrospectively analyzed medical records of 120 individuals seen at the Angelman Syndrome Clinic at Massachusetts General Hospital and 43 individuals seen at the University of North Carolina Comprehensive Angelman Clinic. Read More

    Progressive macrothrombocytopenia and hearing loss in a large family with DIAPH1 related disease.
    Am J Med Genet A 2017 Oct 16;173(10):2826-2830. Epub 2017 Aug 16.
    Department of Otorhinolaryngology-Head and Neck Surgery, University of the Ryukyus, Okinawa, Japan.
    In this study, we describe a Japanese family with progressive hearing loss and macrothrombocytopenia. Using next-generation and Sanger sequencing analyses, we identified a heterozygous variant in exon 27 of the DIAPH1 gene (NM_005219), c.3637C>T, p. Read More

    The role of IQSEC2 in syndromic intellectual disability: Narrowing the diagnostic odyssey.
    Am J Med Genet A 2017 Oct 17;173(10):2814-2820. Epub 2017 Aug 17.
    Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia.
    While X-linked intellectual disability (XLID) syndromes pose a diagnostic challenge for clinicians, an increasing number of recognized disorders and their genetic etiologies are providing answers for patients and their families. The availability of clinical exome sequencing is broadening the ability to identify mutations in genes previously unrecognized as causing XLID. In recent years, the IQSEC2 gene, located at Xp11. Read More

    Diaphanospondylodysostosis and ischiospinal dysostosis, evidence for one disorder with variable expression in a patient who has survived to age 9 years.
    Am J Med Genet A 2017 Oct 17;173(10):2808-2813. Epub 2017 Aug 17.
    Drexel University College of Medicine, Philadelphia, Pennsylvania.
    Diaphanospondylodysostosis (DSD) and ischiospinal dysostosis (ISD) are both rare skeletal dysplasias consisting of abnormal axial skeletal development but normal appendicular skeletal development. Both disorders recently have been found to result from mutations in the BMPER gene. We report a patient with one deletion and one mutation of the BMPER gene who has features most consistent with DSD but who has survived to age 9 years. Read More

    Epilepsy in fragile-X-syndrome mimicking panayiotopoulos syndrome: Description of three patients.
    Am J Med Genet A 2017 Oct 16;173(10):2753-2757. Epub 2017 Aug 16.
    Scientific Institute, IRCCS Eugenio Medea, Conegliano, Treviso, Italy, Epilepsy and Neurophysiology Unit.
    Fragile-X-syndrome is the most common cause of inherited intellectual disability. Epilepsy is reported to occur in 10-20% of individuals with Fragile-X-syndrome. A frequent seizure/electroencephalogram (EEG) pattern resembles that of benign rolandic epilepsy. Read More

    Neonatal fractures as a presenting feature of LMOD3-associated congenital myopathy.
    Am J Med Genet A 2017 Oct 16;173(10):2789-2794. Epub 2017 Aug 16.
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
    Nemaline myopathy is a rare inherited disorder characterized by weakness, hypotonia, and depressed deep tendon reflexes. It is clinically and genetically heterogeneous, with the most severe phenotype presenting as perinatal akinesia, severe muscle weakness, feeding difficulties and respiratory failure, leading to early mortality. Pathogenic variants in 12 genes, encoding components of the sarcomere or factors related to myogenesis, have been reported in patients affected with the disorder. Read More

    Paternal transmission of a FMR1 full mutation allele.
    Am J Med Genet A 2017 Oct 16;173(10):2795-2797. Epub 2017 Aug 16.
    Biochemistry and Molecular Genetics Department, Hospital Clinic, Barcelona, Spain.
    Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and autism. In most of cases, the molecular basis of this syndrome is a CGG repeat expansion in the 5' untranslated region of the FMR1 gene. It is inherited as an X linked dominant trait, with a reduced penetrance (80% for males and 30% for females). Read More

    The pregnancy in neurofibromatosis 1: A retrospective register-based total population study.
    Am J Med Genet A 2017 Oct 16;173(10):2641-2648. Epub 2017 Aug 16.
    University of Turku, Turku, Finland.
    The objective of this retrospective total population study was to form a view of the pregnancies of the patients with neurofibromatosis type 1 (NF1). A cohort of 1,410 Finnish patients with NF1 was acquired by searching NF1-related inpatient and outpatient hospital visits and confirming the diagnoses by reviewing the medical records. Ten matched control persons per patient with NF1 were collected from Population Register Centre. Read More

    Challenges of developing and conducting clinical trials in rare disorders.
    Am J Med Genet A 2017 Aug 16. Epub 2017 Aug 16.
    Office of Drug Evaluation I/Office of New Drugs/CDER/FDA, Silver Spring, Maryland.
    Rare disease drug development is a rapidly expanding field. Clinical researchers in rare diseases face many challenges when conducting trials in small populations. Disease natural history is often poorly understood and the ability to detect clinically meaningful outcomes requires understanding of their rate of occurrence and variability, both of which contribute to difficulties in powering a study. Read More

    The facial morphology in Down syndrome: A 3D comparison of patients with and without obstructive sleep apnea.
    Am J Med Genet A 2017 Aug 17. Epub 2017 Aug 17.
    Down Syndrome Program, Division of Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.
    Obstructive sleep apnea (OSA) occurs at a high prevalence in patients with Down syndrome (DS). A polysomnogram, which is often cumbersome and challenging, remains the gold standard method of diagnosing OSA. OSA in patients with DS is often attributed to skeletal and soft-tissue structural alterations that are characteristic of the DS phenotype; as such, we hypothesized that assessing anthropometric facial measurements may be predictive of OSA in patients with DS. Read More

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