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    7947 results match your criteria American Journal of Medical Genetics Part A[Journal]

    1 OF 159

    Family management of childhood chronic conditions: Does it make a difference if the child has an intellectual disability?
    Am J Med Genet A 2017 Nov 15. Epub 2017 Nov 15.
    University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
    The purpose of this analysis was to assess the applicability of the Family Management Measure (FaMM) to families in which there was a child with an intellectual disability versus a chronic condition. Drawing on data from 571 parents of children with a chronic physical condition and 539 parents of children with Down syndrome, we compared the two groups across the six FaMM scales. After accounting for the covariate effects of race, ethnicity, family income, and child age, we found significant differences in four of the six FaMM scales, with parents of children with Down syndrome reporting a significantly more positive view on the Condition Management Effort and View of Condition Impact scales and a significantly less positive view on the Child's Daily Life and Condition Management Ability scales than parents of children with a chronic physical condition. Read More

    "Minimal" holoprosencephaly in a 14q deletion syndrome patient.
    Am J Med Genet A 2017 Dec;173(12):3216-3220
    Institute of Medical Genetics, Catholic University School of Medicine, Rome, Italy.
    We report on a patient with terminal deletion of the long arm of chromosome 14 displaying brain interhemispheric fusion limited to the midline anterior frontal cortex associated with hypoplastic corpus callosum and incomplete rotation of the left hippocampus in a clinical setting of motor and intellectual disability with poor language, and social behavior abnormalities with aggressiveness. Some possible correlations between clinical signs and symptoms and various aspects of the complex brain malformation are briefly discussed and compared with other known abnormalities of chromosome 14. The different neuropathology of the most common forms and the new forms of holoprosencephaly recently described is also discussed and leads us to suggest classifying the interhemispheric fusion of this case as a "minimal" form of holoprosencephaly. Read More

    Cover Image, Volume 173A, Number 12, December 2017.
    Am J Med Genet A 2017 Dec;173(12)
    NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
    The cover image, by Isabel Hardee et al., is based on the Clinical Report Defective ciliogenesis in INPP5E-related Joubert syndrome, DOI: 10.1002/ajmg. Read More

    Clinical delineation of a subtype of frontonasal dysplasia with creased nasal ridge and upper limb anomalies: Report of six unrelated patients.
    Am J Med Genet A 2017 Dec;173(12):3136-3142
    Equipe GAD, INSERM LNC UMR 1231, Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France.
    Frontonasal dysplasias are rare congenital malformations of frontonasal process-derived structures, characterized by median cleft, nasal anomalies, widely spaced eyes, and cranium bifidum occultum. Several entities of syndromic frontonasal dysplasia have been described, among which, to date, only a few have identified molecular bases. We clinically ascertained a cohort of 124 individuals referred for frontonasal dysplasia. Read More

    A heterozygous mutation in RPGR associated with X-linked retinitis pigmentosa in a patient with Turner syndrome mosaicism (45,X/46,XX).
    Am J Med Genet A 2017 Nov 14. Epub 2017 Nov 14.
    Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
    Turner syndrome with retinitis pigmentosa (RP) is rare, with only three cases reported based on clinical examination alone. We summarized the 4-year follow-up and molecular findings in a 28-year-old patient with Turner syndrome and the typical features of short stature and neck webbing, who also had X-linked RP. Her main complaints were night blindness and progressive loss of vision since the age of 9 years. Read More

    Further delineation of the GDF6 related multiple synostoses syndrome.
    Am J Med Genet A 2017 Nov 12. Epub 2017 Nov 12.
    Department of Genetics, University Medical Center Utrecht, Utrecht, Netherlands.
    A mutation in GDF6 was recently found to underlie a multiple synostoses syndrome. In this report, we describe the second family with GDF6-related multiple synostoses syndrome (SYNS4), caused by a novel c.1287C>A/p. Read More

    How chromosomal deletions can unmask recessive mutations? Deletions in 10q11.2 associated with CHAT or SLC18A3 mutations lead to congenital myasthenic syndrome.
    Am J Med Genet A 2017 Nov 12. Epub 2017 Nov 12.
    AP-HP, Département de Génétique Médicale, Hôpital Armand Trousseau, UPMC, Paris, France.
    A congenital myasthenia was suspected in two unrelated children with very similar phenotypes including several episodes of severe dyspnea. Both children had a 10q11.2 deletion revealed by Single Nucleotide Polymorphisms array or by Next Generation Sequencing analysis. Read More

    DOCK3-related neurodevelopmental syndrome: Biallelic intragenic deletion of DOCK3 in a boy with developmental delay and hypotonia.
    Am J Med Genet A 2017 Nov 12. Epub 2017 Nov 12.
    Division of Human Genetics, Department of Pediatrics, The Children's Hospital, Pennsylvania, Philadelphia.
    Dedicator of cytokinesis (DOCK) family are evolutionary conserved guanine nucleotide exchange factors (GEFs) for the Rho GTPases, Rac, and Cdc42. DOCK3 functions as a GEF for Rac1, and plays an important role in promoting neurite and axonal growth by stimulating actin dynamics and microtubule assembly pathways in the central nervous system. Here we report a boy with developmental delay, hypotonia, and ataxia due to biallelic DOCK3 deletion. Read More

    Expanding the phenotypic spectrum of TP63-related disorders including the first set of monozygotic twins.
    Am J Med Genet A 2017 Nov 12. Epub 2017 Nov 12.
    Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
    Individuals with Tumor Protein P63 (TP63)-related disorders are known to present with a range of phenotypic features, including ectrodactyly, ectodermal dysplasia, cleft lip/palate, Rapp-Hodgkin, Hay-Wells, and limb-mammary syndromes. We present six individuals from three families, including a set of monozygotic twins, with pathogenic TP63 variants who had novel clinical findings. The twins were discordant for cleft lip and palate, and the type of hand malformations, but concordant for choanal atresia, and bilateral volar nail. Read More

    Interstitial microdeletion of 17q11.2 is associated with hypotonia, fatigue, intellectual disability, and a subtle facial phenotype in three unrelated patients.
    Am J Med Genet A 2017 Nov 12. Epub 2017 Nov 12.
    Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
    Over the past decade chromosomal microarray analysis (array CGH) has allowed the discovery of many novel disease-causing recurrent microdeletion and microduplication syndromes. Here we present three unrelated patients (2F; 1M) from three different countries, with developmental delay, intellectual disability, hypotonia, fatigue, and highly similar dysmorphic facial features. Shared facial features are a broad and wide forehead, similar shape of the eyes with long palpebral fissures, a bulbous tip of the nose and thick lips. Read More

    Co-occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines.
    Am J Med Genet A 2017 Nov 12. Epub 2017 Nov 12.
    Children's Hospital of Wisconsin, Down Syndrome Clinic of Wisconsin, Milwaukee, Wisconsin.
    Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. The United States Preventive Service Task Force (USPSTF) has developed criteria for prioritizing conditions of public health importance with the potential for providing screening recommendations to improve clinical care. The quality of existing evidence needed to inform clinical guidelines has not been previously reviewed. Read More

    Familial choreoathetosis due to novel heterozygous mutation in PDE10A.
    Am J Med Genet A 2017 Nov 12. Epub 2017 Nov 12.
    Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India.
    PDE10A encodes a dual cAMP-cGMP phosphodiesterase that is enriched in the medium spiny neurons of the corpus striatum in the brain and plays an important role in basal ganglia circuitry. Three unrelated patients with childhood onset chorea and striatal abnormalities on MRI brain with heterozygous de novo variants in PDE10A have been described previously. Two families with eight affected individuals with biallelic mutations in PDE10A have also been described previously. Read More

    A homozygous deleterious CDK10 mutation in a patient with agenesis of corpus callosum, retinopathy, and deafness.
    Am J Med Genet A 2017 Nov 12. Epub 2017 Nov 12.
    Monique and Jacques Roboh Department of Genetic Research, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
    The primary cilium is a key organelle in numerous physiological and developmental processes. Genetic defects in the formation of this non-motile structure, in its maintenance and function, underlie a wide array of ciliopathies in human, including craniofacial, brain and heart malformations, and retinal and hearing defects. We used exome sequencing to study the molecular basis of disease in an 11-year-old female patient who suffered from growth retardation, global developmental delay with absent speech acquisition, agenesis of corpus callosum and paucity of white matter, sensorineural deafness, retinitis pigmentosa, vertebral anomalies, patent ductus arteriosus, and facial dysmorphism reminiscent of STAR syndrome, a suspected ciliopathy. Read More

    Type 2 Gaucher disease in an infant despite a normal maternal glucocerebrosidase gene.
    Am J Med Genet A 2017 Dec 1;173(12):3211-3215. Epub 2017 Nov 1.
    Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland.
    Gaucher disease (GD) is a recessively inherited autosomal lysosomal storage disease, the most severe of which is type 2, an acute neuronopathic form. We report an affected infant who inherited one mutant allele, Arg257Gln (c.887G>A; p. Read More

    Novel pregnancy-triggered episodes of CAPOS syndrome.
    Am J Med Genet A 2017 Nov 1. Epub 2017 Nov 1.
    Division of Medical Genetics, Department of Medicine, University of Washington Medical Center, Seattle, Washington.
    Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome (OMIM# 601338) is a rare autosomal dominant disorder characterized by episodic, fever-induced ataxic encephalopathy in childhood with residual symptoms. All identified patients have the same heterozygous missense variant c.2452G>A (p. Read More

    STAR syndrome plus: The first description of a female patient with the lethal form.
    Am J Med Genet A 2017 Dec 31;173(12):3226-3230. Epub 2017 Oct 31.
    Department of Pathophysiology and Transplantation, Università degli Studi di Milano and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
    The STAR syndrome is a rare X-linked dominant developmental disorder caused by point mutations in the single FAM58A gene or deletions involving FAM58A and its flanking genes. The STAR phenotype is characterized by a rather homogeneous constellation of facial dysmorphisms and malformations summarized by its acronym, Syndactyly, Telecanthus, Anogenital, and Renal malformations. Here we describe a female patient with STAR syndrome and a 130 kb deletion at Xq28, including the FAM58A gene. Read More

    Aneurysmal bone cysts and pathologic fracture associated with supernumerary ring chromosome 6 in two unrelated patients.
    Am J Med Genet A 2017 Dec 28;173(12):3205-3210. Epub 2017 Oct 28.
    Division of Medical Genetics, Nemours-Alfred I. duPont Hospital for Children, Wilmington, Delaware.
    Small supernumerary ring chromosome 6 (sSRC[6]) is a rare chromosomal abnormality characterized by a broad clinical phenotype. The spectrum of this disorder can range from phenotypically normal to severe developmental delay and congenital anomalies. We describe two unrelated patients with small SRCs derived from chromosome 6 with a novel bone phenotype. Read More

    Cover Image, Volume 173A, Number 11, November 2017.
    Am J Med Genet A 2017 Nov;173(11)
    Genometrics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland.
    The cover image, by Cristina M. Justice et al., is based on the Original Article A Variant Associated with Sagittal Nonsydromic Craniosynostosis Alters the Regulatory Function of a Non-Coding Element, DOI: 10. Read More

    Defective ciliogenesis in INPP5E-related Joubert syndrome.
    Am J Med Genet A 2017 Dec 20;173(12):3231-3237. Epub 2017 Oct 20.
    NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
    Joubert syndrome is a neurodevelopmental disorder, characterized by malformation of the mid and hindbrain leading to the pathognomonic molar tooth appearance of the brainstem and cerebellum on axial MRI. Core clinical manifestations include hypotonia, tachypnea/apnea, ataxia, ocular motor apraxia, and developmental delay of varying degrees. In addition, a subset of patients has retinal dystrophy, chorioretinal colobomas, hepatorenal fibrocystic disease, and polydactyly. Read More

    Novel recessive PDZD7 biallelic mutations in two Chinese families with non-syndromic hearing loss.
    Am J Med Genet A 2017 Oct 19. Epub 2017 Oct 19.
    Chinese PLA Institute of Otolaryngology, Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
    Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous genetic condition. PDZD7 has emerged as a new genetic etiology of ARNSHL. Biallelic mutations in the PDZD7 gene have been reported in two German families, four Iranian families, and a Pakistani family with ARNSHL. Read More

    Beyond Down syndrome phenotype: Paternally derived isodicentric chromosome 21 with partial monosomy 21q22.3.
    Am J Med Genet A 2017 Dec 19;173(12):3153-3157. Epub 2017 Oct 19.
    Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania.
    Inverted isodicentric chromosome 21 is a rare form of chromosomal rearrangement that may result in trisomy 21; sometimes this rearrangement may also lead to segmental monosomy of the terminal long arm of chromosome 21. In this report, we describe the prenatal diagnosis and neonatal follow-up of a child with a paternally derived, de novo isodicentric chromosome 21 and a concurrent ∼1.2 Mb deletion of the 21q22. Read More

    Mutations of KIF5C cause a neurodevelopmental disorder of infantile-onset epilepsy, absent language, and distinctive malformations of cortical development.
    Am J Med Genet A 2017 Dec 19;173(12):3127-3131. Epub 2017 Oct 19.
    Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
    The clinical diagnosis of malformations of cortical development (MCDs) is often challenging due to the complexity of the brain malformation by neuroimaging, the rarity of individual malformation syndromes, and the rapidly evolving genetic landscape of these disorders facilitated with the use of Next Generation Sequencing (NGS) methods. While the clinical and molecular diagnosis of severe cortical malformations, such as classic lissencephaly, is often straightforward, the diagnosis of more subtle and complex types of cortical malformations, such as pachygyria and polymicrogyria (PMG), can be more challenging due to limited knowledge regarding their genetic etiologies. Here, we report two individuals with the same de novo KIF5C mutation who present with subtle MCDs, early onset epilepsy and significant neurodevelopmental and behavioral issues including absent language. Read More

    Biallelicframeshift mutation in RIN2 in a patient with intellectual disability and cataract, without RIN2 syndrome.
    Am J Med Genet A 2017 Dec 19;173(12):3238-3240. Epub 2017 Oct 19.
    Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.

    Longitudinal perspectives on the psychosis spectrum in 22q11.2 deletion syndrome.
    Am J Med Genet A 2017 Oct 19. Epub 2017 Oct 19.
    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
    The prevalence of psychotic disorders in individuals with 22q11.2 Deletion Syndrome (22q11DS) reaches 25-35% in young adulthood and may provide a neurogenetic model for clinical risk of psychotic disorders in the general population. This review focuses on prospective longitudinal studies in 22q11DS, which capture fluctuations in psychosis symptoms over time and may provide insights into potential demographic, clinical, cognitive, and neuroimaging predictors of psychosis-spectrum outcomes in the general population. Read More

    Homozygous indel mutation in CDH11 as the probable cause of Elsahy-Waters syndrome.
    Am J Med Genet A 2017 Dec 8;173(12):3143-3152. Epub 2017 Oct 8.
    Faculty of Medicine, Department of Medical Genetics, Hacettepe University, Ankara, Turkey.
    Two sisters from a consanguineous couple were seen in genetics department for facial dysmorphic features and glaucoma. They both had broad foreheads, hypertelorism, megalocorneas, thick eyebrows with synophrys, flat malar regions, broad and bulbous noses, and mild prognathism. Both had glaucoma, younger one also had cataracts and phthisis bulbi. Read More

    A variant associated with sagittal nonsyndromic craniosynostosis alters the regulatory function of a non-coding element.
    Am J Med Genet A 2017 Nov 6;173(11):2893-2897. Epub 2017 Oct 6.
    Genometrics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland.
    Craniosynostosis presents either as a nonsyndromic congenital anomaly or as a finding in nearly 200 genetic syndromes. Our previous genome-wide association study of sagittal nonsyndromic craniosynostosis identified associations with variants downstream from BMP2 and intronic in BBS9. Because no coding variants in BMP2 were identified, we hypothesized that conserved non-coding regulatory elements may alter BMP2 expression. Read More

    Noncompaction cardiomyopathy in an infant with Walker-Warburg syndrome.
    Am J Med Genet A 2017 Nov 5;173(11):3082-3086. Epub 2017 Oct 5.
    Division of Medical Genetics, Department of Pediatrics, Kingston General Hospital, Queen's University, Kingston, Canada.
    Walker-Warburg syndrome (WWS) is a rare autosomal recessive, congenital muscular dystrophy that is associated with brain and eye anomalies. Several genes encoding proteins involved in α-dystroglycan glycosylation have been implicated in the aetiology of WWS. We describe a patient with nonclassical features of WWS presenting with heart failure related to noncompaction cardiomyopathy resulting in death at 4 months of age. Read More

    BCL11A frameshift mutation associated with dyspraxia and hypotonia affecting the fine, gross, oral, and speech motor systems.
    Am J Med Genet A 2017 Sep 27. Epub 2017 Sep 27.
    Department of Pediatric Neurology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium.
    We report the case of a 7-year-old male of Western European origin presenting with moderate intellectual disability, severe childhood apraxia of speech in the presence of oral and manual dyspraxia, and hypotonia across motor systems including the oral and speech motor systems. Exome sequencing revealed a de novo frameshift protein truncating mutation in the fourth exon of BCL11A, a gene recently demonstrated as being involved in cognition and language development. Making parallels with a previously described patient with a 200 kb 2p15p16. Read More

    Clinical Report: Warsaw Breakage Syndrome with small radii and fibulae.
    Am J Med Genet A 2017 Nov 28;173(11):3075-3081. Epub 2017 Sep 28.
    Division of Genetics, Department of Pediatrics, University of California, San Francisco, California.
    We present two new cases of Warsaw Breakage Syndrome (WABS), an autosomal recessive cohesinopathy, in sisters aged 13 and 11 years who both had compound heterozygous mutations in DDX11. After exclusion of Fanconi anemia, Bloom syndrome and Nijmegen breakage syndrome, whole exome sequencing revealed two novel variants-c.1523T>G, predicting (p. Read More

    Clinical and risk factor analysis of cloacal defects in the National Birth Defects Prevention Study.
    Am J Med Genet A 2017 Nov 28;173(11):2873-2885. Epub 2017 Sep 28.
    Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa.
    Cloacal exstrophy (CE) and persistent cloaca (PC) (alternatively termed urorectal septum malformation sequence [URSMS]), represent two major cloacal defects (CDs). Clinical characteristics and risk factors often are studied for both defects combined, rather than exploring if these defects have different etiologies. We enumerated clinical features for 47 CE and 54 PC (inclusive of URSMS) cases from the National Birth Defects Prevention Study. Read More

    Prenatal diagnosis of femoral facial syndrome: Three case reports and literature review.
    Am J Med Genet A 2017 Nov 26;173(11):2923-2946. Epub 2017 Sep 26.
    Department of Genetics, University Hospital of Amiens, CHU Amiens Sud, Amiens, France.
    Facial femoral syndrome (FFS) is a rare congenital abnormality, also known as femoral hypoplasia-unusual facies syndrome, characterized by variable degrees of femoral hypoplasia, associated with specific facial features. Other organ malformations are sometimes present. Most cases are sporadic, but rare family observations suggest genetic origin. Read More

    Mutations in folate transporter genes and risk for human myelomeningocele.
    Am J Med Genet A 2017 Nov 26;173(11):2973-2984. Epub 2017 Sep 26.
    Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.
    The molecular mechanisms linking folate deficiency and neural tube defect (NTD) risk in offspring remain unclear. Folate transporters (SLC19A1, SLC46A1, SLC25A32, and FOLH1) and folate receptors (FOLR1, FOLR2, and FOLR3) are suggested to play essential roles in transporting folate from maternal intestinal lumen to the developing embryo. Loss of function variants in these genes may affect folate availability and contribute to NTD risk. Read More

    Coexistence of mutations in keratin 10 (KRT10) and the mitochondrial genome in a patient with ichthyosis with confetti and Leber's hereditary optic neuropathy.
    Am J Med Genet A 2017 Nov 25;173(11):3093-3097. Epub 2017 Sep 25.
    Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
    Ichthyosis with confetti (IWC) is a severe congenital genodermatosis characterized by ichthyosiform erythroderma since birth and confetti-like spots of normal skin appearing in childhood as a results of revertant mosaicism. This disorder is caused by mutations in KRT10 or KRT1 genes. We report a 16-year-old boy who presented ichthyosiform erythroderma with severe desquamation since birth and gradually worsening psycho-neurological symptoms (mental retardation, ataxia, dystonia, hypoacusis). Read More

    Finding the genetic mechanisms of folate deficiency and neural tube defects-Leaving no stone unturned.
    Am J Med Genet A 2017 Nov 25;173(11):3042-3057. Epub 2017 Sep 25.
    Division of Medical Genetics, Department of Pediatrics, University of Texas Health Science Houston-McGovern Medical School, Houston, Texas.
    Neural tube defects (NTDs) occur secondary to failed closure of the neural tube between the third and fourth weeks of gestation. The worldwide incidence ranges from 0.3 to 200 per 10,000 births with the United States of American NTD incidence at around 3-6. Read More

    Biallelic mutations in GPD1 gene in a Chinese boy mainly presented with obesity, insulin resistance, fatty liver, and short stature.
    Am J Med Genet A 2017 Dec 25;173(12):3189-3194. Epub 2017 Sep 25.
    Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
    Biallelic mutations in the GPD1 gene cause a rare autosomal recessive inherited disease known as transient infantile hypertriglyceridemia (OMIM #614480). To date, only five pathogenic variants have been reported in 15 patients from three studies. The clinical symptoms of the affected individuals present a certain degree of heterogeneity. Read More

    De novo mutations in HNRNPU result in a neurodevelopmental syndrome.
    Am J Med Genet A 2017 Nov 25;173(11):3003-3012. Epub 2017 Sep 25.
    Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
    Exome sequencing in the context of developmental disorders is a useful technique, but variants found need to be interpreted in the context of detailed phenotypic information. Whole gene deletions and loss-of-function-mutations in the HNRNPU gene have been associated with intellectual disability and seizures in some patients. However, a unifying syndromic phenotype has not been previously elucidated. Read More

    A randomized controlled trial of levodopa in patients with Angelman syndrome.
    Am J Med Genet A 2017 Sep 25. Epub 2017 Sep 25.
    Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts.
    Treatment for Angelman syndrome (AS) is currently limited to symptomatic interventions. A mouse model of AS has reduced calcium/calmodulin-dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long-term potentiation. In a rat model of Parkinson disease, levodopa reduced phosphorylation of various proteins, including calcium/calmodulin-dependent kinase II. Read More

    From clinical observations and molecular dissection to novel therapeutic strategies for primary immunodeficiency disorders.
    Am J Med Genet A 2017 Sep 21. Epub 2017 Sep 21.
    Department of Pediatrics and Seattle Children's Research Institute, University of Washington, Seattle, Washington.
    The field of primary immunodeficiency diseases (PID) is rapidly expanding with more than 300 genetically defined disorders that have been clinically described and molecularly analyzed. The molecular dissection of these entities has led to the discovery of new immunologic pathways and to novel and effective disease-specific therapies. This review provides a summary of these primary immune defects categorized by clinical phenotype and molecular similarity as defined by the International Union of Immunologic Societies (IUIS) Expert Committee for PID. Read More

    Women who carry a fragile X premutation are biologically older than noncarriers as measured by telomere length.
    Am J Med Genet A 2017 Nov 21;173(11):2985-2994. Epub 2017 Sep 21.
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
    Women who carry a fragile X premutation, defined as having 55-200 unmethylated CGG repeats in the 5' UTR of the X-linked FMR1 gene, have a 20-fold increased risk for primary ovarian insufficiency (FXPOI). We tested the hypothesis that women with a premutation + FXPOI have shorter telomeres than those without FXPOI because they are "biologically older." Using linear regression, we found that women carrying a premutation (n = 172) have shorter telomeres and hence, are "biologically older" than women carrying the normal size allele (n = 81). Read More

    The Influence of trisomy 21 on facial form and variability.
    Am J Med Genet A 2017 Nov 21;173(11):2861-2872. Epub 2017 Sep 21.
    Department of Anthropology, The Pennsylvania State University, University Park, Pennsylvania.
    Triplication of chromosome 21 (trisomy 21) results in Down syndrome (DS), the most common live-born human aneuploidy. Individuals with DS have a unique facial appearance that can include form changes and altered variability. Using 3D photogrammatic images, 3D coordinate locations of 20 anatomical landmarks, and Euclidean Distance Matrix Analysis methods, we quantitatively test the hypothesis that children with DS (n = 55) exhibit facial form and variance differences relative to two different age-matched (4-12 years) control samples of euploid individuals: biological siblings of individuals with DS (n = 55) and euploid individuals without a sibling with DS (n = 55). Read More

    A cohort study of multiple families with FBN1 p.R650C variant, ectopia lentis, and low but not absent risk for aortopathy.
    Am J Med Genet A 2017 Nov 21;173(11):2995-3002. Epub 2017 Sep 21.
    The Heart Center, Nationwide Children's Hospital, Columbus, Ohio.
    Marfan syndrome is a multisystem disease with cardiovascular, ophthalmologic, and skeletal features. Diagnosis is made clinically with emphasis on presence of aortic root dilation and ectopia lentis (EL). Most individuals meeting these criteria have a pathogenic variant in FBN1, usually unique or observed rarely. Read More

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