8,940 results match your criteria American Journal of Medical Genetics Part A[Journal]


Evidence of intrauterine growth restriction and growth hormone deficiency in 49,XXXXY syndrome.

Am J Med Genet A 2020 Jul 2. Epub 2020 Jul 2.

Division of Research, The Focus Foundation, Davidsonville, Maryland, USA.

49,XXXXY is an X and Y chromosome variation that occurs in 1:85,000 to 1:100,000 live male births. Previous case studies have described boys with this disorder to be shorter than average when compared with boys with only one extra chromosome and with the mean stature in a small cohort reported to range from the seventh to 33rd percentile. The origin behind the possible differences in height between boys with 47,XXY and 49,XXXXY is currently unknown, however one study hypothesized that it was due to a difference in the expression of the SHOX gene. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61738DOI Listing

A homozygous variant in growth and differentiation factor 2 (GDF2) may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis.

Am J Med Genet A 2020 Jul 2. Epub 2020 Jul 2.

Department of Clinical Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61743DOI Listing

Developmental delay, intellectual disability, short stature, subglottic stenosis, hearing impairment, onychodysplasia of the index fingers, and distinctive facial features: A newly reported autosomal recessive syndrome.

Am J Med Genet A 2020 Jul 2:e61730. Epub 2020 Jul 2.

Aix Marseille University, Inserm, MMG, Marseille, France.

We report on a multiply consanguineous Syrian family where two siblings, a boy and a girl, presented with a compilation of symptoms including developmental delay, severe intellectual disability, absent speech, hearing impairment, short stature, subglottic stenosis, increased length of the palpebral fissures, onychodysplasia of index fingers, scoliosis, genu valgum, and malpositioned toes. Two other individuals from the extended family with similar clinical features are also described. Array-CGH did not reveal any pathological copy number variation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61730DOI Listing

A homozygous truncating NALCN variant in two Afro-Caribbean siblings with hypotonia and dolichocephaly.

Am J Med Genet A 2020 Jul 2. Epub 2020 Jul 2.

Department of Biochemistry, St. George's University School of Medicine, St. George's, Grenada.

NALCN encodes a sodium ion leak channel expressed in the nervous system that conducts a persistent influx of sodium ions to facilitate action potential formation. Homozygous or compound heterozygous loss of function variants in NALCN cause infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1; OMIM 615419). Through exome and Sanger sequencing, we found two siblings of Afro-Caribbean ancestry who are homozygous for a known NALCN pathogenic variant, p. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61744DOI Listing

Variable pulmonary manifestations in Chitayat syndrome: Six additional affected individuals.

Am J Med Genet A 2020 Jun 27. Epub 2020 Jun 27.

Institute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Hand hyperphalangism leading to shortened index fingers with ulnar deviation, hallux valgus, mild facial dysmorphism and respiratory compromise requiring assisted ventilation are the key features of Chitayat syndrome. This condition results from the recurrent heterozygous missense variant NM_006494.2:c. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61735DOI Listing

Associated anomalies in cases with congenital clubfoot.

Am J Med Genet A 2020 Jun 26. Epub 2020 Jun 26.

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

Congenital clubfoot CTEV is a common congenital anomaly, its etiology is unclear and its pathogenesis is controversial. Cases with CTEV often have other non-CTEV associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61721DOI Listing

Prenatal presentation and diagnosis of Baraitser-Winter syndrome using exome sequencing.

Am J Med Genet A 2020 Jun 26. Epub 2020 Jun 26.

Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA.

Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) is a rare autosomal dominant developmental disorder associated with missense mutations in the genes ACTB or ACTG1. The classic presentation of BWCFF is discerned by the combination of unique craniofacial characteristics including ocular coloboma, intellectual disability, and hypertelorism. Congenital contractures and organ malformations are often present, including structural defects in the brain, heart, renal, and musculoskeletal system. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61725DOI Listing

The dark side of COVID-19: The need of integrated medicine for children with special care needs.

Am J Med Genet A 2020 Jun 24. Epub 2020 Jun 24.

Department of Woman and Child Health and Public Health, Center for Rare Diseases and Birth Defects, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61722DOI Listing

Diffuse infantile hepatic hemangiomas in a patient with Beckwith-Wiedemann syndrome: A new association?

Am J Med Genet A 2020 Jun 23. Epub 2020 Jun 23.

Rare Diseases and Clinical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome, caused by alterations in a cluster of imprinted genes located within the chromosome region 11p15.5. Common clinical features are overgrowth, macroglossia, lateralized overgrowth, abdominal wall defects, neonatal hypoglycemia and an increased risk of embryonal tumors, such as hepatoblastomas. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61718DOI Listing

Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia.

Am J Med Genet A 2020 Jun 23. Epub 2020 Jun 23.

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

Esophageal atresia (EA) is a congenital anomaly occurring in 2.3 per 10,000 live births. Due to advances in prenatal imaging, EA is more readily diagnosed, but data on the associated genetic diagnoses, other anomalies, and postnatal outcome for fetuses diagnosed prenatally with EA are scarce. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61639DOI Listing

TUBB3 E410K syndrome: Case report and review of the clinical spectrum of TUBB3 mutations.

Am J Med Genet A 2020 Jun 23. Epub 2020 Jun 23.

Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS Rome, Rome, Italy.

The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The β-tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron-specific expression pattern. A recurrent heterozygous mutation, c. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61719DOI Listing

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing.

Am J Med Genet A 2020 Jun 23. Epub 2020 Jun 23.

Department of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61641DOI Listing

Confirming TBC1D32-related ciliopathy in humans.

Am J Med Genet A 2020 Jun 23. Epub 2020 Jun 23.

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61717DOI Listing

Lipoplexes Could be Alternative to Viral Vectors in Gene Therapy.

Authors:

Am J Med Genet A 2020 Jul;182(7):1548-1549

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61241DOI Listing

Absence of Functional ACTL6B Gene is Potential Cause of Recessive Autism.

Authors:

Am J Med Genet A 2020 Jul;182(7):1549-1550

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61726DOI Listing

Improvement in ventriculomegaly following cervicomedullary decompressive surgery in children with achondroplasia and foramen magnum stenosis.

Am J Med Genet A 2020 Jun 11. Epub 2020 Jun 11.

Maxine Dunitz Neurosugical Institute-Department of Neurological Surgery, Cedars-Sinai Medial Center, Los Angeles, California, USA.

The role of cervicomedullary decompression (CMD) in the care of hydrocephalic achondroplastic children who present with simultaneous foramen magnum stenosis is not well understood. We sought to determine the percentage of symptomatic achondroplastic children with foramen magnum stenosis who had stabilization or improvement in ventriculomegaly following CMD. The authors retrospectively reviewed the records of pediatric patients at Cedars-Sinai Medical Center with achondroplasia and signs of progressive ventriculomegaly who underwent CMD for symptomatic foramen magnum stenosis between the years 2000 and 2018. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61640DOI Listing

Kabuki syndrome with midgut malrotation and hyperinsulinemic hypoglycemia: A rare co-occurrence from Thailand.

Am J Med Genet A 2020 Jun 11. Epub 2020 Jun 11.

Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Kabuki syndrome (KS) is a rare heterogeneous phenotypic genetic syndrome, characterized by hypotonia, developmental delay and/or intellectual disability with typical facial features. It is challenging to diagnose KS in newborn and young infant. We report a Thai girl who presented with two rare co-occurrence phenotypes, hyperinsulinemic hypoglycemia and midgut malrotation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61723DOI Listing

Differentiating molecular etiologies of Angelman syndrome through facial phenotyping using deep learning.

Am J Med Genet A 2020 Jun 11. Epub 2020 Jun 11.

Department of Genetic Medicine, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Angelman syndrome (AS) is caused by several genetic mechanisms that impair the expression of maternally-inherited UBE3A through deletions, paternal uniparental disomy (UPD), UBE3A pathogenic variants, or imprinting defects. Current methods of differentiating the etiology require molecular testing, which is sometimes difficult to obtain. Recently, computer-based facial analysis systems have been used to assist in identifying genetic conditions based on facial phenotypes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61720DOI Listing

Going forward in a new world.

Am J Med Genet A 2020 Jul 9;182(7):1553-1554. Epub 2020 Jun 9.

Washington, District of Columbia, USA.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61715DOI Listing

Maternal SLE and brachytelephalangic chondrodysplasia punctata in a patient with unrelated de novo RAF1 and SIX2 variants.

Am J Med Genet A 2020 Jul 7;182(7):1807-1811. Epub 2020 Jun 7.

The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

Our improved tools to identify the aetiologies in patients with multiple abnormalities resulted in the finding that some patients have more than a single genetic condition and that some of the diagnoses made in the past are acquired rather than inherited. However, limited knowledge has been accumulated regarding the phenotypic outcome of the interaction between different genetic conditions identified in the same patients. We report a newborn girl with brachytelephalangic chondrodysplasia punctata (BCDP) as well as frontonasal dysplasia, ptosis, bilateral hearing loss, vertebral anomalies, and pulmonary hypoplasia who was found, by whole exome sequencing, to have a de novo pathogenic variant in RAF1 (c. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61621DOI Listing

Baraitser-Winter cerebrofrontofacial syndrome: Report of two adult siblings.

Am J Med Genet A 2020 Jun 7. Epub 2020 Jun 7.

Division of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.

Baraitser-Winter cerebrofrontofacial syndrome (BWCS) is a rare, autosomal dominant condition that is characterized by intellectual disability, distinctive craniofacial features, structural brain abnormalities, seizures, microcephaly, hearing loss, and ocular colobomas. The first three cases were described in 1988 by Baraitser and Winter and included two siblings and an unrelated third patient. Subsequently, causative missense variants in the ACTB and ACTG1 genes were identified, with de novo occurrence in patients with the condition. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61637DOI Listing

Characterization of sleep habits and medication outcomes for sleep disturbance in children and adults with Angelman syndrome.

Am J Med Genet A 2020 Jun 7. Epub 2020 Jun 7.

Harvard Medical School, Boston, Massachusetts, USA.

The objectives of this study were to characterize the sleep habits of 50 clinically referred individuals with Angelman syndrome (AS) and to retrospectively compare the effectiveness/tolerability of the three most commonly prescribed sleep medications in the sample. An experienced physician assigned a Clinical Global Impressions-Severity scale (CGI-S) score for each subject's AS-specific symptoms. Caregivers completed the Child Sleep Habits Questionnaire (CSHQ; screen for sleep problems in school-aged [4-10 years] children), a screening assessment for sleep problems. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61642DOI Listing

Activating variants in PDGFRB result in a spectrum of disorders responsive to imatinib monotherapy.

Am J Med Genet A 2020 Jul 5;182(7):1576-1591. Epub 2020 Jun 5.

Division of Genetic Medicine, University of Washington, Seattle, Washington, USA.

More than 50 individuals with activating variants in the receptor tyrosine kinase PDGFRB have been reported, separated based on clinical features into solitary myofibromas, infantile myofibromatosis, Penttinen syndrome with premature aging and osteopenia, Kosaki overgrowth syndrome, and fusiform aneurysms. Despite their descriptions as distinct clinical entities, review of previous reports demonstrates substantial phenotypic overlap. We present a case series of 12 patients with activating variants in PDGFRB and review of the literature. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61615DOI Listing

Long-term follow-up of an individual with ITPR1-related disorder.

Am J Med Genet A 2020 Jul 4;182(7):1846-1847. Epub 2020 Jun 4.

Department of Translational Medicine, Federico II University, Naples, Italy.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61609DOI Listing

Characteristic dental pattern with hypodontia and short roots in Fraser syndrome.

Am J Med Genet A 2020 Jul 2;182(7):1681-1689. Epub 2020 Jun 2.

Institute of Human Genetics, University Hospital, Magdeburg, Germany.

Fraser syndrome (FS) is a rare autosomal recessive multiple congenital malformation syndrome characterized by cryptophthalmos, cutaneous syndactyly, renal agenesis, ambiguous genitalia, and laryngotracheal anomalies. It is caused by biallelic mutations of FRAS1, FREM2, and GRIP1 genes, encoding components of a protein complex that mediates embryonic epithelial-mesenchymal interactions. Anecdotal reports have described abnormal orodental findings in FS, but no study has as yet addressed the orodental findings of FS systematically. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61610DOI Listing

Clinical characteristics and quality of life, depression, and anxiety in adults with neurofibromatosis type 1: A nationwide study.

Am J Med Genet A 2020 Jul 2;182(7):1704-1715. Epub 2020 Jun 2.

Psychological Aspects of Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark.

Neurofibromatosis type 1 (NF1) is a genetic condition characterized by numerous somatic manifestations. The psychosocial burden in adults has rarely been studied. We examined the prevalence of self-reported impairment of quality of life (QoL), symptoms of anxiety and depression and need for support, associated with disease severity and visibility. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61627DOI Listing

Here and now.

Am J Med Genet A 2020 Jun 1. Epub 2020 Jun 1.

Abdulaziz International School, Riyadh, Saudi Arabia.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61622DOI Listing

Ectrodactyly-ectodermal dysplasia-clefting syndrome presenting with bilateral choanal atresia and rectal stenosis.

Am J Med Genet A 2020 May 31. Epub 2020 May 31.

Clinical Genetics, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK.

We present the case of a male who shortly after birth developed acute respiratory distress due to bilateral choanal atresia, following which he was found to have rectal stenosis. Genetic testing for CHARGE syndrome was negative, but whole genome sequencing identified heterozygosity for a pathogenic missense variant in TP63 (c.727C > T, p. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61628DOI Listing

A case report of Noonan syndrome-like disorder with loose anagen hair 2 treated with recombinant human growth hormone.

Am J Med Genet A 2020 Jun 1. Epub 2020 Jun 1.

Growth, Development, and Mental health of Children and Adolescence Center, Children's Hospital of Chongqing Medical University, Chongqing, China.

Protein phosphatase 1 catalytic subunit beta (PPP1CB) is a disease-causing gene of Noonan-like syndrome, which acts via the RAS/MAPK pathway. To date, only 17 patients diagnosed with PPP1CB-related Noonan-like syndrome have been reported around the world, with few reports in Asia. Twelve reported patients are of short stature and only one patient was treated with growth hormone (GH); however, follow-up data is lacking. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61638DOI Listing

Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome.

Am J Med Genet A 2020 Jul 31;182(7):1690-1696. Epub 2020 May 31.

Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy.

Cornelia de Lange syndrome (CdLS), Rubinstein-Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61611DOI Listing

Expanding the phenotype of biallelic RNPC3 variants associated with growth hormone deficiency.

Am J Med Genet A 2020 May 28. Epub 2020 May 28.

Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Pathogenic variants in components of the minor spliceosome have been associated with several human diseases. Recently, it was reported that biallelic RNPC3 variants lead to severe isolated growth hormone deficiency and pituitary hypoplasia. The RNPC3 gene codes for the U11/U12-65K protein, a component of the minor spliceosome. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61632DOI Listing

Ectopia lentis in Loeys-Dietz syndrome type 4.

Am J Med Genet A 2020 May 28. Epub 2020 May 28.

Division of Medical Genetics, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.

Loeys-Dietz syndrome is a heritable disorder of the connective tissue leading to multisystem involvement including craniofacial features, skeletal abnormalities, cutaneous findings and early-onset and aggressive disease of the aorta and its branches. There are multiple types of Loeys-Dietz syndrome related to pathogenic variants in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3. Individuals with Loeys-Dietz syndrome may be misdiagnosed as having Marfan syndrome due to shared phenotypic features and aortic root dilation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61633DOI Listing

Genetic Variants May Play Role in Opioid Dependence.

Authors:

Am J Med Genet A 2020 06;182(6):1296-1297

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61612DOI Listing

Neurodevelopmental Disorder Defined in TET3-Deficient Individuals.

Authors:

Am J Med Genet A 2020 06;182(6):1295-1296

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61235DOI Listing

Familial dilated cardiomyopathy associated with pathogenic TBX5 variants: Expanding the cardiac phenotype associated with Holt-Oram syndrome.

Am J Med Genet A 2020 Jul 25;182(7):1725-1734. Epub 2020 May 25.

West of Scotland Clinical Genetics Service, Queen Elizabeth University Hospital, Glasgow, UK.

Holt-Oram syndrome (HOS) is a rare, autosomal dominant disorder caused by heterozygous pathogenic variants in cardiac T-box transcription factor, TBX5. Classically, it is associated with upper limb malformations and variable cardiac abnormalities. Limb manifestations are considered to be invariably present, ranging in severity from limitation in movement, to triphalangeal thumbs, absent thumbs, shortened forearms, or phocomelia. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61635DOI Listing

Parent perceptions, beliefs, and fears around genetic treatments and cures for children with Angelman syndrome.

Am J Med Genet A 2020 Jul 25;182(7):1716-1724. Epub 2020 May 25.

Centre for Clinical Trials in Rare Neurodevelopmental Disorders, Children's Health Queensland, Brisbane, Queensland, Australia.

Genetic therapies have shown recent promise in alleviating some of the cognitive issues associated with some genetic disorders; however, these therapies may come with significant health and socio-ethical concerns, particularly when they involve child participants. Little is known about what parents of children with genetic disorders think about genetic therapies, or about their knowledge of how genetic-based therapy might treat their child's symptoms. Forty-two parents of children with Angelman syndrome (AS) and 27 parents of a mixed etiology comparison group completed an online survey reporting on their perceptions of, and priorities for, genetic therapy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61631DOI Listing

Recessive ACO2 variants as a cause of isolated ophthalmologic phenotypes.

Am J Med Genet A 2020 May 25. Epub 2020 May 25.

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

The mitochondrial aconitase gene (ACO2) encodes an enzyme that catalyzes the conversion of citrate to isocitrate in the tricarboxylic acid cycle. Biallelic variants in ACO2 are purported to cause two distinct disorders: infantile cerebellar-retinal degeneration (ICRD) which is characterized by CNS abnormalities, neurodevelopmental phenotypes, optic atrophy and retinal degeneration; and optic atrophy 9 (OPA9), characterized by isolated ophthalmologic phenotypes including optic atrophy and low vision. However, some doubt remains as to whether biallelic ACO2 variants can cause isolated ophthalmologic phenotypes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61634DOI Listing
May 2020
2.159 Impact Factor

The burden of chronic disease, multimorbidity, and polypharmacy in adults with Down syndrome.

Am J Med Genet A 2020 Jul 25;182(7):1735-1743. Epub 2020 May 25.

Centro Medicina dell'Invecchiamento, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, and Università Cattolica del Sacro Cuore, Rome, Italy.

Data on clinical characteristics of adults with Down syndrome (DS) are limited and the clinical phenotype of these persons is poorly described. This study aimed to describe the occurrence of chronic diseases and pattern of medication use in a population of adults with DS. Participants were 421 community dwelling adults with DS, aged 18 years or older. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61636DOI Listing

Fulminant myocarditis following recurrent generalized erythrokeratoderma in a child with a heterozygous GJA1 variant.

Am J Med Genet A 2020 May 25. Epub 2020 May 25.

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

Pathogenic germline variants in the gap junction protein alpha 1 (GJA1) gene have been identified in several congenital disorders affecting cutaneous, skeletal, and cardiac tissues. Here, we describe a 12-year-old patient with a GJA1 c.113G>A, p. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61626DOI Listing

A pathogenic variant in the SETBP1 hotspot results in a forme-fruste Schinzel-Giedion syndrome.

Am J Med Genet A 2020 May 22. Epub 2020 May 22.

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.

Schinzel-Giedion syndrome (SGS; OMIM 269150) is an ultra-rare genetic disorder associated with a distinctive facial gestalt, congenital malformations, severe intellectual disability, and a progressive neurological course. The prognosis for SGS is poor, with survival beyond the first decade rare. Germline, de novo heterozygous variants in the SETBP1 gene cause SGS with the pathogenic variants associated with the SGS phenotype missense and confined to exon 4 of the gene, clustered in a four amino acid (12 bp) hotspot in the SKI homologous region of the SETBP1 protein. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61630DOI Listing

Sacral protuberance with cleft lip and palate: Prenatal presentation of 3MC syndrome.

Am J Med Genet A 2020 Jul 22;182(7):1812-1814. Epub 2020 May 22.

Division of Maternal Fetal Medicine, School of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.

3MC syndromes are rare heterogeneous autosomal recessive conditions previously designated as Mingarelli, Malpuech, Michels, and Carnevale syndromes, characterized by dysmorphic facial features, facial clefts, growth restriction, and intellectual disability. 3MC is secondary to mutations in the MASP1, MASP3, COLEC11, and COLEC10 genes. The number of patients with 3MC syndrome with known mutations in the COLEC11 or MASP1 is, to date, less than 50. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61624DOI Listing

Nissen fundoplication in Cornelia de Lange syndrome spectrum: Who are the potential candidates?

Am J Med Genet A 2020 Jul 21;182(7):1697-1703. Epub 2020 May 21.

Department of Pediatrics, ASST-Lariana, "Sant'Anna" Hospital, Como, Italy.

Cornelia de Lange spectrum (CdLSp) is a rare genetic condition characterized by intellectual disability, facial dysmorphisms, major malformations, growth impairment, and development delay. Approximately 80% of CdLSp patients have gastroesophageal reflux disease (GERD) with a varied clinical presentation. The aim of this study is to define potential clinical/genetic risk factors based on the clinical phenotype description of CdLSp patients with severe GERD who underwent surgical treatment. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61625DOI Listing

Bi-allelic loss-of-function novel variants in LTBP3-related skeletal dysplasia: Report of first patient from India.

Am J Med Genet A 2020 May 20. Epub 2020 May 20.

Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Dental anomalies and short stature (DASS) has been recently identified as a distinct entity, associated with bi-allelic hypomorphic variants in LTBP3 gene. Only 20 individuals from nine families have been previously reported, with a consistent phenotype of short stature, brachyolmia, and amelogenesis imperfecta. We report the first case from India, with novel radiographic and molecular findings in LTBP3 gene, thereby expanding the phenotypic spectrum of DASS. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61629DOI Listing

Genotype and phenotype correlation in a family with a 2q37 deletion downstream of HDAC4.

Am J Med Genet A 2020 May 20. Epub 2020 May 20.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília, Brasília, Brazil.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61620DOI Listing

Love in the time of COVID-19.

Am J Med Genet A 2020 06 19;182(6):1299-1301. Epub 2020 May 19.

American College of Medical Genetics and Genomics, Bethesda, Maryland.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276842PMC

An apparent new syndrome of extreme short stature, microcephaly, dysmorphic faces, intellectual disability, and a bone dysplasia of unknown etiology.

Am J Med Genet A 2020 Jul 19;182(7):1562-1571. Epub 2020 May 19.

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

We report on a 26-year-old male with extreme short stature, microcephaly, macroglossia, other dysmorphic features, severe intellectual disability, and a bone dysplasia. The patient had an extensive genetic and biochemical evaluation that was all normal or noninformative. Recently, the proband died following a period of not eating. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61619DOI Listing

Novel de novo TRIP12 mutation reveals variable phenotypic presentation while emphasizing core features of TRIP12 variations.

Am J Med Genet A 2020 Jul 19;182(7):1801-1806. Epub 2020 May 19.

University of Newcastle, Callaghan, New South Wales, Australia.

Intellectual disability (ID) is a complicated and multifactorial condition often with an unclear cause. Advancements in diagnostic techniques have identified genetic causes in a significant proportion. Pathogenic variants in TRIP12, encoding for an E3 ligand in the ubiquitin-protease pathway, have previously been identified as a cause of ID with autistic behavior and dysmorphic features. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61618DOI Listing

Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in MBTPS1.

Am J Med Genet A 2020 Jul 18;182(7):1796-1800. Epub 2020 May 18.

McKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Variants in MBTPS1 (membrane-bound transcription factor peptidase, site 1) encoding the protein convertase site-1 protease (S1P) were recently reported in a single individual with skeletal dysplasia and elevated plasma lysosomal enzymes. Here, we report the second individual with this newly described autosomal recessive spondyloepiphyseal dysplasia (OMIM #618392), presenting severe growth retardation, cataract and dysmorphic features, mainly retromicrognathia. Epilepsy and craniosynostosis were novel findings in our proband. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61614DOI Listing

Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: Mismapping due to the pseudogene SBDSP1.

Am J Med Genet A 2020 Jul 15;182(7):1631-1636. Epub 2020 May 15.

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

Shwachman-Diamond syndrome characterized by metaphyseal dysplasia, pancreatic insufficiency, and pancytopenia is caused by biallelic mutations in SBDS. Gene conversion between SBDS and its pseudogene SBDSP1 is the major cause. Here, we report two unrelated patients with Shwachman-Diamond syndrome who were shown to be compound heterozygotes for relatively frequent pathogenic alleles (the 258+2T>C allele and another allele composed of 183-184TA>CT and 201A>G) using an established polymerase chain reaction sequencing assay with SBDS-specific primers. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61598DOI Listing

SMG9-deficiency syndrome caused by a homozygous missense variant: Expanding the genotypic and phenotypic spectrum of this developmental disorder.

Am J Med Genet A 2020 Jul 15;182(7):1829-1831. Epub 2020 May 15.

Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61616DOI Listing