8,447 results match your criteria American Journal of Medical Genetics Part A[Journal]


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

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

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

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

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http://dx.doi.org/10.1002/ajmg.a.61108DOI Listing

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Acute leukemia in a patient with 15q overgrowth syndrome.

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

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

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

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http://dx.doi.org/10.1002/ajmg.a.61115DOI Listing

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

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

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

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

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http://dx.doi.org/10.1002/ajmg.a.61111DOI Listing

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

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

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

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

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http://dx.doi.org/10.1002/ajmg.a.61074DOI Listing
March 2019
2 Reads

Genotype and phenotype correlation in 103 individuals with 2q37 deletion syndrome reveals incomplete penetrance and supports HDAC4 as the primary genetic contributor.

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

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

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

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http://dx.doi.org/10.1002/ajmg.a.61089DOI Listing
March 2019
2 Reads

SATB2-associated syndrome in patients from Japan: Linguistic profiles.

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

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

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

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http://dx.doi.org/10.1002/ajmg.a.61114DOI Listing
March 2019
1 Read

Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis.

Am J Med Genet A 2019 Mar 5. Epub 2019 Mar 5.

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

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

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http://dx.doi.org/10.1002/ajmg.a.61076DOI Listing

Patient with anomalous skin pigmentation expands the phenotype of ARID2 loss-of-function disorder, a SWI/SNF-related intellectual disability.

Am J Med Genet A 2019 Mar 5. Epub 2019 Mar 5.

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

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

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

Identification of a deletion containing TBX4 in a neonate with acinar dysplasia by rapid exome sequencing.

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

Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington.

We describe a neonate with severe respiratory failure due to acinar dysplasia found by rapid exome sequencing (rES), to have a deletion containing the TBX4 gene. rES can affect patient management in the intensive care unit and should be considered in concert with lung biopsy in neonates with undifferentiated respiratory failure. Read More

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http://dx.doi.org/10.1002/ajmg.a.61096DOI Listing

Female-restricted syndromic intellectual disability in a patient from Thailand.

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

Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Female-restricted syndromic intellectual disability (ID) is a neurodevelopmental disorder with developmental delay (DD)/ID, facial dysmorphism, and diverse congenital anomalies comprising heart defects, anal anomalies, choanal atresia, postaxial polydactyly, scoliosis, and brain abnormalities. Loss-of-function mutations in the USP9X gene inherited as X-linked dominance were identified as its etiology in females of different ethnic groups. Here, we report a 15-year-old Thai girl harboring a novel de novo heterozygous one-base pair deletion (c. Read More

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http://dx.doi.org/10.1002/ajmg.a.61106DOI Listing
March 2019
1 Read

Parents' perspective on having a child with Down Syndrome in France.

Authors:
Remi Bertrand

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

Samut Prakan, Thailand.

In 2011, Skotko, Levine, and Goldstein asked parents who had children with Down Syndrome (DS) in the United States how they felt about having a child with DS. The purpose of the present study was to ask the same questions to parents living in France so that this information could be shared with new and expectant parents. The results were also compared to the findings of Skotko, Levine, and Goldstein (2011a) to see whether some parental feelings might be universally shared and to discuss the differences observed. Read More

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http://dx.doi.org/10.1002/ajmg.a.61102DOI Listing

Cardiac valvular Ehlers-Danlos syndrome is a well-defined condition due to recessive null variants in COL1A2.

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

Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.

Cardiac valvular Ehlers-Danlos syndrome (EDS) is a rare EDS subtype, caused by specific recessive variants in the gene encoding pro-α2-chain of type I collagen (COL1A2). Cardiac valvular EDS is mainly characterized by generalized/peripheral joint hypermobility, moderate-severe cardiac valvular disease, skin hyperextensibility and other minor soft tissues features. Only five molecularly confirmed patients have been reported to date. Read More

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http://dx.doi.org/10.1002/ajmg.a.61100DOI Listing
March 2019
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Managing the need to tell: Triggers and strategic disclosure of thalassemia major in Singapore.

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

Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

This study explored patients' experiences and perceptions of living with thalassemia (an inherited hematologic disorder), perceptions of social stigma, and impact on disclosure decision-making. Semistructured, in-person interviews were conducted in Singapore with 30 individuals: 16 thalassemia major patients and 14 parents of children with thalassemia. Findings were indicative of felt or enacted stigma that may have influenced disclosure decisions. Read More

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http://doi.wiley.com/10.1002/ajmg.a.61107
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http://dx.doi.org/10.1002/ajmg.a.61107DOI Listing
March 2019
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Identification of a novel homozygous variant confirms ITPA as a developmental and epileptic encephalopathy gene.

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

Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.

ITPA related epileptic encephalopathy (epileptic encephalopathy, early infantile, 35) is a rare inborn error of metabolism. All reported individuals with this condition, including the present case manifest global developmental delay, seizures, progressive postnatal microcephaly, hypotonia, thin corpus callosum, cerebral atrophy, delayed myelination and white matter changes in posterior limb of internal capsule. Cataract and dilated cardiomyopathy are other characteristic findings. Read More

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http://doi.wiley.com/10.1002/ajmg.a.61103
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http://dx.doi.org/10.1002/ajmg.a.61103DOI Listing
February 2019
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Evolution of the phenotype of craniosynostosis with dental anomalies syndrome and report of IL11RA variant population frequencies in a Crouzon-like autosomal recessive syndrome.

Am J Med Genet A 2019 Apr 27;179(4):668-673. Epub 2019 Feb 27.

Department of Pediatrics and Human Development, Michigan State University College of Human Medicine, Grand Rapids, Michigan.

In 2011, biallelic loss-of-function variants in the interleukin receptor 11 alpha gene IL11RA were found to be associated with a Crouzon-like craniosynostosis syndrome with associated dental anomalies (CRSDA). Since then, a total of 41 similar patients have been reported with IL11RA variants. We report two adult brothers diagnosed with Crouzon syndrome as children, in which the clinical diagnosis of CRSDA was made on reevaluation. Read More

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http://dx.doi.org/10.1002/ajmg.a.61070DOI Listing
April 2019
2 Reads
2.159 Impact Factor

A De novo HDAC2 variant in a patient with features consistent with Cornelia de Lange syndrome phenotype.

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

Department of Pediatrics, Division of Medical Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.

Cornelia de Lange syndrome (CdLS) is an autosomal dominant genetic disorder caused by pathogenic variants in NIPBL, RAD21, SMC3, HDAC8, or SMC1A; all of which code for proteins that are components of, or interact with, the cohesin complex. Despite the identification of multiple genes associated with CdLS, over 25% of individuals strongly suspected to have CdLS have negative genetic testing, indicating that there are additional genes associated with the condition. HDAC2 codes for histone deacetylase 2 (HDAC2) and, like HDAC8, is a Class 1 histone deacetylase. Read More

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http://dx.doi.org/10.1002/ajmg.a.61101DOI Listing
February 2019

A 2q24.2 microdeletion containing TANK as novel candidate gene for intellectual disability.

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

Institute of Human Genetics, Otto-von-Guericke University, Magdeburg, Germany.

Interstitial deletions within the chromosomal region 2q24.2 have already been linked to intellectual disability (ID) in the past. In most cases the described patients showed a syndromic form of ID associated with large deletions containing multiple genes. Read More

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http://dx.doi.org/10.1002/ajmg.a.61093DOI Listing
February 2019
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Disruption of the PTHLH regulatory landscape results in features consistent with hyperparathyroid disease.

Am J Med Genet A 2019 Apr 25;179(4):663-667. Epub 2019 Feb 25.

Division of Clinical and Metabolic Genetics and University of Toronto, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.

Parathyroid hormone like hormone (PTHLH) signaling is essential for the proper formation of bone and its elevation or disruption has been directly implicated in several different skeletal dysplasias. We report a patient with a 2.802 Mb deletion upstream of the PTHLH coding sequence who presents with multiple fractures, metaphyseal changes, and overall features consistent with hyperparathyroid like disease. Read More

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http://doi.wiley.com/10.1002/ajmg.a.61071
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http://dx.doi.org/10.1002/ajmg.a.61071DOI Listing
April 2019
2 Reads

The Society for Craniofacial Genetics and Developmental Biology 41st Annual Meeting.

Am J Med Genet A 2019 Feb 22. Epub 2019 Feb 22.

Stowers Institute for Medical Research, Kansas City, Missouri.

The mission of the Society for Craniofacial Genetics and Developmental Biology (SCGDB) is to promote education, research, and communication about normal and abnormal development of the tissues and organs of the head. The SCGDB welcomes as members undergraduate students, graduate students, postdoctoral researchers, medical and dental practitioners, scientists, and academicians who possess an interest in craniofacial biology. Each year our members come together to share their novel findings, build upon, and challenge current knowledge of craniofacial biology. Read More

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http://dx.doi.org/10.1002/ajmg.a.61090DOI Listing
February 2019

Spontaneous pneumothorax and hemothorax frequently precede the arterial and intestinal complications of vascular Ehlers-Danlos syndrome.

Am J Med Genet A 2019 Feb 22. Epub 2019 Feb 22.

Division of Medical Genetics, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas.

Vascular Ehlers-Danlos syndrome (vEDS) is a connective tissue disorder due to defective type III collagen production and is associated with arterial rupture, spontaneous intestinal perforation, and gravid uterine rupture. Spontaneous pneumothorax and/or hemothorax (P/HTX) also occurs in vEDS patients. The temporal relation of pulmonary manifestations to arterial and intestinal complications in vEDS has not been well described. Read More

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http://dx.doi.org/10.1002/ajmg.a.61094DOI Listing
February 2019

EED and EZH2 constitutive variants: A study to expand the Cohen-Gibson syndrome phenotype and contrast it with Weaver syndrome.

Am J Med Genet A 2019 Apr 21;179(4):588-594. Epub 2019 Feb 21.

Department of Clinical Genetics, St George's University of London, London, United Kingdom.

Overgrowth-intellectual disability (OGID) syndromes are characterized by increased growth (height and/or head circumference ≥+2 SD) in association with an intellectual disability. Constitutive EED variants have previously been reported in five individuals with an OGID syndrome, eponymously designated Cohen-Gibson syndrome and resembling Weaver syndrome. Here, we report three additional individuals with constitutive EED variants, identified through exome sequencing of an OGID patient series. Read More

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http://dx.doi.org/10.1002/ajmg.a.61066DOI Listing
April 2019
1 Read

Okamoto syndrome has features overlapping with Au-Kline syndrome and is caused by HNRNPK mutation.

Authors:
Nobuhiko Okamoto

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

Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan.

Okamoto syndrome is characterized by severe intellectual disability, generalized hypotonia, stenosis of the ureteropelvic junction with hydronephrosis, cardiac anomalies, and characteristic facial gestalt. Several patients have been reported. The basic mechanism of Okamoto syndrome has not been clarified. Read More

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http://dx.doi.org/10.1002/ajmg.a.61079DOI Listing
February 2019
1 Read

Retinoic acid receptor beta variant-related colonic hypoganglionosis.

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

Department of Surgery, Division of Pediatrics, Saint Louis University School of Medicine, Saint Louis, Missouri.

Retinoic acid receptor beta (RARB) variants are heavily linked to pathologies of neural crest cell migration. The purpose of this report is to present a 23-month-old male with the previously described R387C RARB gain-of-function variant whose gastrointestinal issues and long-term constipation lead to the discovery of colonic hypoganglionosis. This case further delineates the pattern of malformation associated with RARB variants. Read More

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http://dx.doi.org/10.1002/ajmg.a.61078DOI Listing
February 2019
1 Read

Klippel-Feil syndrome as a novel feature of Schimke immunoosseous dysplasia.

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

Department of Paediatrics, Midland Regional Hospital, Mullingar, County Westmeath, Ireland.

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http://dx.doi.org/10.1002/ajmg.a.61087DOI Listing
February 2019

Expanding the genetic and clinical spectrum of the NONO-associated X-linked intellectual disability syndrome.

Am J Med Genet A 2019 Feb 17. Epub 2019 Feb 17.

Division of Medical Genetics, University of Utah, Salt Lake City, Utah.

The NONO gene encodes a nuclear protein involved in RNA metabolism. Hemizygous loss-of-function NONO variants have been associated with syndromic intellectual disability and with left ventricular noncompaction (LVNC). A two-year-old boy presented to the University of Utah's Penelope Undiagnosed Disease Program with developmental delay, nonfamilial features, relative macrocephaly, and dilated cardiomyopathy with LVNC and Ebstein anomaly. Read More

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http://dx.doi.org/10.1002/ajmg.a.61091DOI Listing
February 2019
4 Reads

Homozygous variant in OTX2 and possible genetic modifiers identified in a patient with combined pituitary hormone deficiency, ocular involvement, myopathy, ataxia, and mitochondrial impairment.

Am J Med Genet A 2019 Feb 17. Epub 2019 Feb 17.

Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Here we report on a singleton patient affected by a complicated congenital syndrome characterized by growth delay, retinal dystrophy, sensorineural deafness, myopathy, ataxia, combined pituitary hormone deficiency, associated with mitochondrial impairment. Targeted clinical exome sequencing led to the identification of a homozygous missense variant in OTX2. Since only dominant mutations within OTX2 have been associated with cases of syndromic microphthalmia, retinal dystrophy with or without pituitary dysfunctions, this represents the first report of an OTX2 recessive mutation. Read More

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http://dx.doi.org/10.1002/ajmg.a.61092DOI Listing
February 2019
1 Read

NID1 variant associated with occipital cephaloceles in a family expressing a spectrum of phenotypes.

Am J Med Genet A 2019 Feb 17. Epub 2019 Feb 17.

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

Autosomal dominant Dandy-Walker malformation and occipital cephalocele (ADDWOC) is a rare, congenital, and incompletely penetrant malformation that is considered to be part of the Dandy-Walker spectrum of disorders. Affected individuals often present with an occipital cephalocele with a bony skull defect, but typically have normal neurological development. Here, we report on a three-generation family in which individuals have variable phenotypes that are consistent with the ADDWOC spectrum: arachnoid cysts in the proband and his maternal grandfather, an occipital cephalocele in the proband and his brother, and a small bony defect in the proband's mother. Read More

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http://doi.wiley.com/10.1002/ajmg.a.61095
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http://dx.doi.org/10.1002/ajmg.a.61095DOI Listing
February 2019
4 Reads

CNOT2 as the critical gene for phenotypes of 12q15 microdeletion syndrome.

Am J Med Genet A 2019 Apr 15;179(4):659-662. Epub 2019 Feb 15.

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

Chromosome 12q15 microdeletion syndrome is characterized by intellectual disability and dysmorphic facial features, but the associations between each of the deleted genes and the phenotypes of 12q15 microdeletion syndrome remain unclear. Recently, the smallest region of overlap in 16 previously reported patients was used to define three candidate genes for the 12q15 microdeletion syndrome: CNOT2, KCNMB4, and PTPRB. Among these three candidate genes, CNOT2 maintains the structural integrity of the carbon catabolite repressor 4 (CCR4)-negative on TATA (NOT) complex, which plays a key role in regulating global gene expression, and is essential for the enzymatic activity of the CCR4-NOT complex. Read More

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http://doi.wiley.com/10.1002/ajmg.a.61068
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http://dx.doi.org/10.1002/ajmg.a.61068DOI Listing
April 2019
4 Reads

Mutations in IFT80 cause SRPS Type IV. Report of two families and review.

Am J Med Genet A 2019 Apr 14;179(4):639-644. Epub 2019 Feb 14.

Reference Center for Skeletal Dysplasia, AP-HP, Necker-Enfants Malades Hospital, Paris, France.

We report novel causative mutations in the IFT80 gene identified in four fetuses from two unrelated families with Beemer-Langer syndrome (BLS) or BLS-like phenotypes. We discuss the implication of the IFT80 gene in ciliopathies, and its diagnostic value for BLS among other SRPS. Read More

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http://dx.doi.org/10.1002/ajmg.a.61050DOI Listing

Prevalence of pathogenic and likely pathogenic variants in the RASopathy genes in patients who have had panel testing for cardiomyopathy.

Am J Med Genet A 2019 Apr 14;179(4):608-614. Epub 2019 Feb 14.

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

RASopathies are a group of developmental disorders caused by pathogenic variants in the RAS-MAPK pathway. Cardiomyopathy is a major feature of this group of disorders, specifically hypertrophic cardiomyopathy (HCM). HCM can be the first presenting feature in individuals with RASopathies. Read More

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http://dx.doi.org/10.1002/ajmg.a.61072DOI Listing
April 2019
1 Read

ERF-related craniosynostosis: The phenotypic and developmental profile of a new craniosynostosis syndrome.

Am J Med Genet A 2019 Apr 13;179(4):615-627. Epub 2019 Feb 13.

Clinical Genetics Service, Great Ormond Street Hospital, London, United Kingdom.

Mutations in the ERF gene, coding for ETS2 repressor factor, a member of the ETS family of transcription factors cause a recently recognized syndromic form of craniosynostosis (CRS4) with facial dysmorphism, Chiari-1 malformation, speech and language delay, and learning difficulties and/or behavioral problems. The overall prevalence of ERF mutations in patients with syndromic craniosynostosis is around 2%, and 0.7% in clinically nonsyndromic craniosynostosis. Read More

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http://dx.doi.org/10.1002/ajmg.a.61073DOI Listing
April 2019
2 Reads

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia.

Am J Med Genet A 2019 Apr 10;179(4):534-541. Epub 2019 Feb 10.

Tulane Center for Aging, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Read More

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http://dx.doi.org/10.1002/ajmg.a.61049DOI Listing
April 2019
2 Reads

Congenital clubfoot in Europe: A population-based study.

Am J Med Genet A 2019 Apr 10;179(4):595-601. Epub 2019 Feb 10.

Paediatric Department, Hospital Lillebaelt Kolding, Kolding, Denmark.

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995-2011. Read More

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http://dx.doi.org/10.1002/ajmg.a.61067DOI Listing
April 2019
8 Reads

Xq22.3q23 microdeletion harboring TMEM164 and AMMECR1 genes: Two case reports confirming a recognizable phenotype with short stature, midface hypoplasia, intellectual delay, and elliptocytosis.

Am J Med Genet A 2019 Apr 8;179(4):650-654. Epub 2019 Feb 8.

Département de Génétique et Procréation, Centre Hospitalo-Universitaire Grenoble Alpes, Grenoble Cedex, France.

The AMME syndrome defined as the combination of Alport syndrome, intellectual disability, midface hypoplasia, and elliptocytosis (AMME) is known to be a contiguous gene syndrome associated with microdeletions in the region Xq22.3q23. Recently, using exome sequencing, missense pathogenic variants in AMMECR1 have been associated with intellectual disability, midface hypoplasia, and elliptocytosis. Read More

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http://dx.doi.org/10.1002/ajmg.a.61057DOI Listing
April 2019
1 Read

Substantial pain burden in frequency, intensity, interference and chronicity among children and adults with neurofibromatosis Type 1.

Am J Med Genet A 2019 Apr 8;179(4):602-607. Epub 2019 Feb 8.

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

Tumor growths, migraine headaches, and other health-related complications reported in patients with neurofibromatosis type 1 (NF1) are often associated with pain. Thus, this study sought to describe and quantify the pain experience in children and young adults with NF1. Surveys were administered to 49 participants (28 children and 21 adults), ages 8 through 40 years. Read More

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http://dx.doi.org/10.1002/ajmg.a.61069DOI Listing
April 2019
3 Reads

Confirmation of a new phenotype in an individual with a variant in the last part of exon 30 of CREBBP.

Am J Med Genet A 2019 Apr 8;179(4):634-638. Epub 2019 Feb 8.

Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato (CA), Italy.

We report here a novel de novo missense variant affecting the last amino acid of exon 30 of CREBBP [NM_004380, c.5170G>A; p.(Glu1724Lys)] in a 17-year-old boy presenting mild intellectual disability and dysmorphisms but not resembling the phenotype of classical Rubinstein-Taybi syndrome. Read More

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http://dx.doi.org/10.1002/ajmg.a.61052DOI Listing

De novo DDX3X missense variants in males appear viable and contribute to syndromic intellectual disability.

Am J Med Genet A 2019 Apr 7;179(4):570-578. Epub 2019 Feb 7.

Manchester Centre for Genomic Medicine, Manchester, United Kingdom.

DDX3X (Xp11.4) encodes a DEAD-box RNA helicase that escapes X chromosome inactivation. Pathogenic variants in DDX3X have been shown to cause X-linked intellectual disability (ID) (MRX102, MIM: 300958). Read More

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http://dx.doi.org/10.1002/ajmg.a.61061DOI Listing
April 2019
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Revealing the functions of novel mutations in RAB3GAP1 in Martsolf and Warburg micro syndromes.

Am J Med Genet A 2019 Apr 7;179(4):579-587. Epub 2019 Feb 7.

Department of Medical Genetics, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey.

Purpose: Martsolf (MS) and Warburg micro syndromes (WARBM) are rare autosomal recessive inherited allelic disorders, which share similar clinical features including microcephaly, intellectual disability, brain malformations, ocular abnormalities, and spasticity. Here, we revealed the functions of novel mutations in RAB3GAP1 in a Turkish female patient with MS and two siblings with WARBM. We also present a review of MS patients as well as all reported RAB3GAP1 pathogenic mutations in the literature. Read More

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http://dx.doi.org/10.1002/ajmg.a.61065DOI Listing
April 2019
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39th Annual David W. Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2018 Annual Meeting.

Am J Med Genet A 2019 Feb 6:674-746. Epub 2019 Feb 6.

Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

The 39th Annual David W. Smith workshop on Malformations and Morphogenesis was held from August 24th-29th 2018 at the Banff Centre for Arts and Creativity, Banff, Alberta, Canada. The Workshop, which honors the legacy of David W. Read More

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http://dx.doi.org/10.1002/ajmg.a.61063DOI Listing
February 2019
2 Reads

Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations.

Am J Med Genet A 2019 Apr 4;179(4):542-551. Epub 2019 Feb 4.

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

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features and intellectual disability caused by haploinsufficiency of the NSD1 gene. Genotype-phenotype correlations have been observed, with major anomalies seen more frequently in patients with 5q35 deletions than those with point mutations in NSD1. Though endocrine features have rarely been described, transient hyperinsulinemic hypoglycemia (HI) of the neonatal period has been reported as an uncommon presentation of Sotos syndrome. Read More

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http://dx.doi.org/10.1002/ajmg.a.61062DOI Listing
April 2019
6 Reads

Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.

Am J Med Genet A 2019 Apr 4;179(4):655-658. Epub 2019 Feb 4.

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

The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by perturbations in signal transduction at the neuromuscular junction. Defects in muscle, skeletal, receptor tyrosine kinase (MuSK) cause two distinct phenotypes: fetal akinesia with multiple congenital anomalies (Fetal akinesia deformation sequence [MIM:208150]) and early onset congenital myasthenia (myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency [MIM:616325]). Myasthenia due to MuSK deficiency has variable clinical features, ranging from a milder presentation of isolated late-onset proximal muscle weakness; to a severe presentation of prenatal-onset diffuse weakness, ophthalmoplegia, respiratory failure, and vocal cord paralysis (VCP). Read More

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http://dx.doi.org/10.1002/ajmg.a.61060DOI Listing
April 2019
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Beckwith-Wiedemann syndrome in diverse populations.

Am J Med Genet A 2019 Apr 4;179(4):525-533. Epub 2019 Feb 4.

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

Beckwith-Wiedemann syndrome (BWS) is the most common epigenetic overgrowth disorder and presents with patients affected by a variety of clinical features. Although genotype-phenotype correlations have been demonstrated in BWS and although BWS has been reported to occur equally among racial and ethnic backgrounds, no study to date has evaluated the frequency of findings in different backgrounds. In this study, we evaluated the incidence of clinical features and molecular diagnoses among patients with BWS in Caucasian, Mixed, and non-Caucasian groups. Read More

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http://dx.doi.org/10.1002/ajmg.a.61053DOI Listing
April 2019
2 Reads