8,139 results match your criteria American Journal of Medical Genetics Part A[Journal]


MAP2K2 mutation as a cause of cardio-facio-cutaneous syndrome in an infant with a severe and fatal course of the disease.

Am J Med Genet A 2018 May 25. Epub 2018 May 25.

Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.

Cardio-facio-cutaneous syndrome (CFCS), a rare congenital disorder of RASopathies, displays high phenotypic variability. Complications during pregnancy and in the perinatal period are commonly reported. Polyhydramnios is observed in over half of pregnancies and might occur with fetal macrocephaly, macrosomia, and/or heart defects. Read More

View Article
May 2018
4 Reads

Piepkorn type of osteochondrodysplasia: Defining the severe end of FLNB-related skeletal disorders in three fetuses and a 106-year-old exhibit.

Am J Med Genet A 2018 May 23. Epub 2018 May 23.

Institute of Pathology, Philipps University of Marburg, Marburg, Germany.

The Piepkorn type of lethal osteochondrodysplasia (POCD) is a rare and lethal dwarfing condition. Four cases have been reported to date. The characteristic features are distinctly shortened "flipper-like" limbs, polysyndactyly, excessive underossification, especially of the limb bones and vertebrae, and large (giant) chondrocytes in the cartilaginous bone primordia. Read More

View Article

Neuropsychiatric expression and catatonia in 22q11.2 deletion syndrome: An overview and case series.

Am J Med Genet A 2018 May 19. Epub 2018 May 19.

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Individuals with 22q11.2 deletion syndrome (22q11.2DS) are at elevated risk of developing treatable psychiatric and neurological disorders, including anxiety disorders, schizophrenia, seizures, and movement disorders, often beginning in adolescence or early to mid-adulthood. Read More

View Article

The first reported case of an inherited pathogenic CHD2 variant in a clinically affected mother and daughter.

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

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

Pathogenic variants in CHD2 (chromodomain helicase DNA-binding protein 2) have been reported in neurodevelopmental disorders with a broad spectrum of phenotypic variability, ranging from mild intellectual disability to atonic-myoclonic epilepsy. However, given the paucity of reported cases the extent of this phenotypic spectrum is currently unknown. Furthermore, all confirmed pathogenic CHD2 variants reported to date have been de novo, preventing the study of intrafamilial phenotypic heterogeneity and creating ambiguity regarding recurrence risk, penetrance, and expressivity. Read More

View Article

Systemic lupus erythematosus in a patient with Noonan syndrome-like disorder with loose anagen hair 1: More than a chance association.

Am J Med Genet A 2018 May 7. Epub 2018 May 7.

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

Systemic lupus erythematosus (SLE) has been reported among patients with RASopathy. Five patients have been reported: three with SHOC2 variants, one with a PTPN11 variant, and one with a KRAS variant. SHOC2 variant might represent a relatively common predisposing factor for SLE among the RASopathy genes. Read More

View Article

Acute lymphoblastic leukemia in a male with Simpson-Golabi-Behmel syndrome.

Am J Med Genet A 2018 May 7. Epub 2018 May 7.

Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.

View Article
May 2018
1 Read

Two Angelman families with unusually advanced neurodevelopment carry a start codon variant in the most highly expressed UBE3A isoform.

Am J Med Genet A 2018 May 7. Epub 2018 May 7.

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

We present three children from two unrelated families with Angelman syndrome (AS) whose developmental skills are far more advanced than any other non-mosaic AS individual ever reported. All have normal gait and use syntactic language spontaneously to express their needs. All of them have a c. Read More

View Article
May 2018
2 Reads

Tissue-specific mosaicism in hereditary hemorrhagic telangiectasia: Implications for genetic testing in families.

Am J Med Genet A 2018 May 7. Epub 2018 May 7.

ARUP Institute for Clinical and Experimental Pathology, University of Utah, Salt Lake City, Utah.

Mosaicism in hemorrhagic telangiectasia (HHT) has been previously identified when testing blood samples of HHT patients. We report the first detection of mosaicism not involving blood of a family proband, and discuss implications for genetic testing algorithms in HHT families. Sanger sequencing and large deletion/duplication analysis in a patient with HHT identified no pathogenic variant in ENG, ACVRL1, or SMAD4. Read More

View Article

Novel PLS3 variants in X-linked osteoporosis: Exploring bone material properties.

Am J Med Genet A 2018 May 7. Epub 2018 May 7.

Academic Unit of Child Health, University of Sheffield, UK.

Background: Idiopathic Juvenile Osteoporosis (IJO) refers to significantly lower than expected bone mass manifesting in childhood with no identifiable aetiology. IJO classically presents in early pubertal period with multiple fractures including metaphyseal and vertebral crush fractures, and low bone-mass.

Methods: Here we describe two patients and provide information on their clinical phenotype, genotype and bone material analysis in one of the patients. Read More

View Article

KIF16B is a candidate gene for a novel autosomal-recessive intellectual disability syndrome.

Am J Med Genet A 2018 May 7. Epub 2018 May 7.

Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (MNGHA), Riyadh, Saudi Arabia.

Intellectual disability (ID) and global developmental delay are closely related; the latter is reserved for children under the age of 5 years as it is challenging to reliably assess clinical severity in this population. ID is a common condition, with up to 1%-3% of the population being affected and leading to a huge social and economic impact. ID is attributed to genetic abnormalities most of the time; however, the exact role of genetic involvement in ID is yet to be determined. Read More

View Article
May 2018
3 Reads
2.16 Impact Factor

Timothy syndrome-like condition with syndactyly but without prolongation of the QT interval.

Am J Med Genet A 2018 May 7. Epub 2018 May 7.

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

Timothy syndrome is characterized by a unique combination of a prolongation of the corrected QT interval of the electrocardiogram and bilateral cutaneous syndactyly of the fingers and the toes and is caused by heterozygous mutations in CACNA1C, a gene encoding a calcium channel. After the discovery of the CACNA1C gene as the causative gene for Timothy syndrome, patients with CACNA1C mutations with QT prolongation but without syndactyly were described. Here, we report a 5-year-old female patient with cutaneous syndactyly, developmental delay, and pulmonary hypertension. Read More

View Article

Sleep disturbances in Rett syndrome: Impact and management including use of sleep hygiene practices.

Am J Med Genet A 2018 Apr 28. Epub 2018 Apr 28.

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

Sleep disturbances are debilitating for individuals with Rett syndrome (RTT) and their families yet the evidence base for management is poor. We investigated management strategies and their relationships with sleep problems. Data were provided by 364/461 (79%) families with a child with RTT and registered with the International RTT Phenotype Database. Read More

View Article

A sibling pair with cardiofaciocutaneous syndrome (CFC) secondary to BRAF mutation with unaffected parents-the first cases of gonadal mosaicism in CFC?

Am J Med Genet A 2018 Apr 28. Epub 2018 Apr 28.

Department of Paediatrics and Child Health, Cork University Hospital, Cork, Ireland.

Cardiofaciocutaneous (CFC) syndrome is a RASopathy characterized by intellectual disability, congenital heart defects, a characteristic facial appearance, gastro-intestinal complications, ectodermal abnormalities and growth failure. The RASopathies result from germline mutations in the Ras/Mitogen-activated-protein-kinase (MAPK) pathway. CFC is associated with mutations in BRAF, KRAS, MEK1 and MEK2. Read More

View Article
April 2018
2 Reads

Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness.

Am J Med Genet A 2018 Apr 28. Epub 2018 Apr 28.

Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

Congenital myasthenic syndrome (CMS) is a heterogeneous disorder that causes fatigable muscle weakness. CMS has been associated with variants in the MuSK gene and, to date, 16 patients have been reported. MuSK-CMS patients present a different phenotypic pattern of limb girdle weakness. Read More

View Article

Loss of function IFT27 variants associated with an unclassified lethal fetal ciliopathy with renal agenesis.

Am J Med Genet A 2018 Apr 27. Epub 2018 Apr 27.

Unité d'Embryofoetopathologie, Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.

Ciliopathies comprise a group of clinically heterogeneous and overlapping disorders with a wide spectrum of phenotypes ranging from prenatal lethality to adult-onset disorders. Pathogenic variants in more than 100 ciliary protein-encoding genes have been described, most notably those involved in intraflagellar transport (IFT) which comprises two protein complexes, responsible for retrograde (IFT-A) and anterograde transport (IFT-B). Here we describe a fetus with an unclassified severe ciliopathy phenotype including short ribs, polydactyly, bilateral renal agenesis, and imperforate anus, with compound heterozygosity for c. Read More

View Article

Atypical presentations associated with non-polyalanine repeat PHOX2B mutations.

Am J Med Genet A 2018 Apr 28. Epub 2018 Apr 28.

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

Congenital central hypoventilation syndrome (CCHS) is a disorder of ventilatory control and autonomic dysregulation that can be caused by mutations in the paired-like homeobox 2B (PHOX2B) gene. The majority of CCHS cases are caused by polyalanine repeat mutations (PARMs) in PHOX2B; however, in rare cases, non-polyalanine repeat mutations (NPARMs) have been identified. Here, we report two patients with NPARMs in PHOX2B. Read More

View Article
April 2018
1 Read

Familial autosomal dominant severe ankyloglossia with tooth abnormalities.

Am J Med Genet A 2018 Apr 28. Epub 2018 Apr 28.

Service de Génétique Médicale, CHU de Nantes, Nantes, France.

Ankyloglossia is a congenital oral anomaly characterized by the presence of a hypertrophic and short lingual frenulum. Mutations in the gene encoding the transcription factor TBX22 have been involved in isolated ankyloglossia and X-linked cleft palate. The knockout of Lgr5 in mice results in ankyloglossia. Read More

View Article

A missense mutation in EBF2 was segregated with imperforate anus in a family across three generations.

Am J Med Genet A 2018 Apr 28. Epub 2018 Apr 28.

Department of Microbiology, Integrated Research Center for Genome Polymorphism, Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.

The etiology of imperforate anus, a major phenotype of anorectal malformation (ARM), is still unknown and not a single gene has been reported to be associated with it. We studied a Korean family with six affected members with imperforate anus across three generations by whole exome sequencing and identified a missense mutation in the EBF2 gene (c.215C > T; p. Read More

View Article
April 2018
2 Reads

A German-Jewish refugee in Vichy France 1939-1941. Arno Motulsky's memoir of life in the internment camps at St. Cyprien and Gurs.

Authors:
Arno G Motulsky

Am J Med Genet A 2018 Jun 26;176(6):1289-1295. Epub 2018 Apr 26.

Departments of Medicine (Medical Genetics) and Genome Sciences, University of Washington, Seattle, Washington.

View Article

Association of 17q24.2-q24.3 deletions with recognizable phenotype and short telomeres.

Am J Med Genet A 2018 Jun 25;176(6):1438-1442. Epub 2018 Apr 25.

Department of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic.

Microdeletions of 17q24.2-q24.3 have been described in several patients with developmental and speech delay, growth retardation, and other features. Read More

View Article

X-linked intellectual disability update 2017.

Am J Med Genet A 2018 Jun 25;176(6):1375-1388. Epub 2018 Apr 25.

J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, South Carolina.

The X-chromosome comprises only about 5% of the human genome but accounts for about 15% of the genes currently known to be associated with intellectual disability. The early progress in identifying the X-linked intellectual disability (XLID)-associated genes through linkage analysis and candidate gene sequencing has been accelerated with the use of high-throughput technologies. In the 10 years since the last update, the number of genes associated with XLID has increased by 96% from 72 to 141 and duplications of all 141 XLID genes have been described, primarily through the application of high-resolution microarrays and next generation sequencing. Read More

View Article

Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions.

Am J Med Genet A 2018 Jun 25;176(6):1398-1404. Epub 2018 Apr 25.

Department of Pediatrics, University of Washington, Seattle, Washington.

Congenital central hypoventilation syndrome (CCHS) is a neurocristopathy caused by pathogenic heterozygous variants in the gene paired-like homeobox 2b (PHOX2B). It is characterized by severe infantile alveolar hypoventilation. Individuals may also have diffuse autonomic nervous system dysfunction, Hirschsprung disease and neural crest tumors. Read More

View Article

KBG syndrome patient due to 16q24.3 microdeletion presenting with a paratesticular rhabdoid tumor: Coincidence or cancer predisposition?

Am J Med Genet A 2018 Jun 25;176(6):1449-1454. Epub 2018 Apr 25.

Department of Human Genetics, Hannover Medical School, Hannover, Germany.

KBG syndrome is a rare autosomal dominant disorder caused by constitutive haploinsufficiency of the ankyrin repeat domain-containing protein 11 (ANKRD11) being the result of either loss-of-function gene variants or 16q24.3 microdeletions. The syndrome is characterized by a variable clinical phenotype comprising a distinct facial gestalt and variable neurological involvement. Read More

View Article
June 2018
2 Reads

Delayed peak response of cortisol to insulin tolerance test in patients with Prader-Willi syndrome.

Am J Med Genet A 2018 Jun 25;176(6):1369-1374. Epub 2018 Apr 25.

Nakagawanosato Ryoiku Center, Saitama, Japan.

Deaths among children with Prader-Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus-pituitary-adrenal (HPA) axis remains unclear. Read More

View Article
June 2018
1 Read

The ontogeny of Robin sequence.

Am J Med Genet A 2018 Jun 25;176(6):1349-1368. Epub 2018 Apr 25.

Royal Children's Hospital, Murdoch Children's Research Institute, Parkville, Australia.

The triad of micrognathia, glossoptosis, and concomitant airway obstruction defined as "Robin sequence" (RS) is caused by oropharyngeal developmental events constrained by a reduced stomadeal space. This sequence of abnormal embryonic development also results in an anatomical configuration that might predispose the fetus to a cleft palate. RS is heterogeneous and many different etiologies have been described including syndromic, RS-plus, and isolated forms. Read More

View Article
June 2018
5 Reads

An assessment of health, social, communication, and daily living skills of adults with Down syndrome.

Am J Med Genet A 2018 Jun 25;176(6):1389-1397. Epub 2018 Apr 25.

Department of Genetics and Genome Sciences, University Hospitals Case Medical Center, Cleveland, Ohio.

Adults with Down syndrome (DS) are surviving longer, yet data delineating life skills are lacking. As providers are encouraged to provide a "balanced" description of DS to family members/caregivers, more quantitative data are required to accurately describe the abilities and potential of adults with DS. This study assessed health, social, communication, and daily living skills of adults with DS to describe the range of abilities and to show how increasing age contributes to functional abilities. Read More

View Article

Mutations in SZT2 result in early-onset epileptic encephalopathy and leukoencephalopathy.

Am J Med Genet A 2018 Jun 25;176(6):1443-1448. Epub 2018 Apr 25.

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Early-onset epileptic encephalopathies (EOEEs) are a genetically heterogeneous collection of severe epilepsies often associated with psychomotor regression. Mutations in SZT2, a known seizure threshold regulator gene, are a newly identified cause of EOEE. We present an individual with EOEE, macrocephaly, and developmental regression with compound heterozygous mutations in SZT2 as identified by whole exome sequencing. Read More

View Article

Neurodevelopmental outcome in 22q11.2 deletion syndrome and management.

Am J Med Genet A 2018 Apr 25. Epub 2018 Apr 25.

University Medical Centre Utrecht, Utrecht, The Netherlands.

The 22q11.2 deletion syndrome (22q11.2 DS) places affected individuals at an increased risk for neurodevelopmental/cognitive, behavioral and social-emotional difficulties. Read More

View Article

The phenotypic spectrum of Xia-Gibbs syndrome.

Am J Med Genet A 2018 Jun 25;176(6):1315-1326. Epub 2018 Apr 25.

Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.

Xia-Gibbs syndrome (XGS: OMIM # 615829) results from de novo truncating mutations within the AT-Hook DNA Binding Motif Containing 1 gene (AHDC1). To further define the phenotypic and molecular spectrum of this disorder, we established an XGS Registry and recruited patients from a worldwide pool of approximately 60 probands. Additional de novo truncating mutations were observed among 25 individuals, extending both the known number of mutation sites and the range of positions within the coding region that were sensitive to alteration. Read More

View Article
June 2018
1 Read

38th Annual David W. Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2017 Annual Meeting.

Am J Med Genet A 2018 Apr 25:1463-1536. Epub 2018 Apr 25.

Division of Human Genetics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania.

The 38th Annual David W. Smith Workshop on Malformations and Morphogenesis occurred on August 26th - 29th, 2017 at the Stoweflake Resort and Conference Center in Stowe, VT. The Workshop, which honors the legacy of David W Smith, brought together clinicians and researchers interested in congenital malformations and their underlying mechanisms of morphogenesis. Read More

View Article

Functional independence of Taiwanese children with Prader-Willi syndrome.

Am J Med Genet A 2018 Jun 25;176(6):1309-1314. Epub 2018 Apr 25.

Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.

Prader-Willi syndrome (PWS) is a genetic disorder with obesity, developmental delay, short stature, and behavioral abnormalities. The study aimed to assess the functional independence in children with PWS. The Functional Independence Measure for Children (WeeFIM) was used to evaluate 81 children with PWS (44 boys and 37 girls) with a median age of 11 years 1 month (range 2 years 8 months to 20 years 2 months) were recruited between January 2013 and December 2016. Read More

View Article
June 2018
1 Read

Complex phenotype of dyskeratosis congenita and mood dysregulation with novel homozygous RTEL1 and TPH1 variants.

Am J Med Genet A 2018 Jun 25;176(6):1432-1437. Epub 2018 Apr 25.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health, Rockville, Maryland.

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome caused by germline mutations in telomere biology genes. Patients have extremely short telomeres for their age and a complex phenotype including oral leukoplakia, abnormal skin pigmentation, and dysplastic nails in addition to bone marrow failure, pulmonary fibrosis, stenosis of the esophagus, lacrimal ducts and urethra, developmental anomalies, and high risk of cancer. We evaluated a patient with features of DC, mood dysregulation, diabetes, and lack of pubertal development. Read More

View Article
June 2018
7 Reads

Arno G. Motulsky, 1923-2018, Luck and Service.

Authors:
John M Opitz

Am J Med Genet A 2018 Jun 25;176(6):1285-1288. Epub 2018 Apr 25.

Departments of Pediatrics (Medical Genetics), Pathology, Human Genetics, Obstetrics & Gynecology, University of Utah School of Medicine, Salt Lake City, Utah.

View Article

Angelman syndrome in adolescence and adulthood: A retrospective chart review of 53 cases.

Am J Med Genet A 2018 Jun 25;176(6):1327-1334. Epub 2018 Apr 25.

Angelman Syndrome Clinic, Massachusetts General Hospital, Boston, Massachusetts.

Angelman syndrome is a neurogenetic disorder with varying clinical presentations and symptoms as the individual ages. The goal of this study was to characterize changes over time in the natural history of this syndrome in a large population. We reviewed the medical records of the 53 patients who were born prior to 2000 and seen at the Angelman Syndrome Clinic at Massachusetts General Hospital to assess neurological, sleep, behavioral, gastrointestinal, orthopedic, and ophthalmologic functioning. Read More

View Article

Clinical spectrum of KIAA2022 pathogenic variants in males: Case report of two boys with KIAA2022 pathogenic variants and review of the literature.

Am J Med Genet A 2018 Jun 25;176(6):1455-1462. Epub 2018 Apr 25.

Department of Pediatrics, Queen's University, Kingston, Ontario, Canada.

KIAA2022 is an X-linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Read More

View Article

Safety and efficacy of noncardiac surgical procedures in the management of patients with trisomy 13: A single institution-based detailed clinical observation.

Am J Med Genet A 2018 May;176(5):1137-1144

Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.

Intensive treatment including surgery for patients with trisomy 13 (T13) remains controversial. This study aimed to evaluate the safety and efficacy of noncardiac surgical intervention for T13 patients. Medical records of patients with karyotypically confirmed T13 treated in the neonatal intensive care unit in Nagano Children's Hospital from January 2000 to October 2016 were retrospectively reviewed, and data from patients who underwent noncardiac surgery were analyzed. Read More

View Article
May 2018
1 Read

Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient.

Am J Med Genet A 2018 May;176(5):1049-1054

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

WDR45 gene-associated neurodegeneration with brain iron accumulation (NBIA), referred to as beta-propeller protein-associated neurodegeneration (BPAN), is a rare disorder that presents with a very nonspecific clinical phenotype in children constituting global developmental delay. This case report illustrates the power of a combination of trio exome sequencing, in silico splicing analysis, and mRNA analysis to provide sufficient evidence for pathogenicity of a relatively intronic variant in WDR45, and in so doing, find a genetic diagnosis for a 6-year-old patient with developmental delay and seizures, a diagnosis which may otherwise have only been found once the characteristic MRI patterns of the disease became more obvious in young adulthood. Read More

View Article
May 2018
1 Read

Giant umbilical cord and hypoglycemia in an infant with Proteus syndrome.

Am J Med Genet A 2018 May;176(5):1222-1224

Department of Pediatrics, University of Yamanashi, Yamanashi, Japan.

Proteus syndrome (PS) is characterized by the progressive, segmental, or patchy overgrowth of the skin, and other tissues. This is the first case report of recurrent severe insulin-independent hypoglycemia in an infant with PS. Somatic p. Read More

View Article
May 2018
3 Reads

Van Maldergem syndrome and Hennekam syndrome: Further delineation of allelic phenotypes.

Am J Med Genet A 2018 May;176(5):1166-1174

Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Biallelic variants in FAT4 are associated with the two disorders, Van Maldergem syndrome (VMS) (n = 11) and Hennekam syndrome (HS) (n= 40). Both conditions are characterized by a typical facial gestalt and mild to moderate intellectual disability, but differ in the occurrence of neonatal hypotonia and feeding problems, hearing loss, tracheal anomalies, and osteopenia in VMS, and lymphedema in HS. VMS can be caused by autosomal recessive variants in DCHS1 as well, and HS can also be caused by autosomal recessive variants in CCBE1 and ADAMTS3. Read More

View Article

Lethal persistent pulmonary hypertension of the newborn in Bohring-Opitz syndrome.

Am J Med Genet A 2018 May;176(5):1245-1248

Genetic Counseling Room, Kagoshima University Hospital, Kagoshima, Japan.

Bohring-Opitz syndrome (BOS) is a rare disease with a number of characteristic features, including hypertelorism, prominent metopic suture, exophthalmos, cleft palate, abnormal posture, and developmental retardation. Here, we report a BOS patient presenting with lethal persistent pulmonary hypertension of the newborn (PPHN) and inspiratory respiratory failure. The female infant was treated with nitric oxide and vasodilator, which did not improve her condition. Read More

View Article

Comparison of perinatal factors in deletion versus uniparental disomy in Prader-Willi syndrome.

Am J Med Genet A 2018 May;176(5):1161-1165

Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, California.

Prader-Willi syndrome (PWS) is caused by a deficiency of imprinted genes in the 15q11-q13 region and is characterized by prenatal onset of hypotonia, poor feeding, childhood-onset obesity, hyperphagia, short stature, facial dysmorphism, intellectual disability, and behavioral problems. We studied perinatal factors in a cohort of 64 people with PWS resulting from paternal deletion of 15q11-q13 and maternal uniparental disomy (UPD) for chromosome 15. We recruited 34 individuals with deletion and 30 with UPD. Read More

View Article
May 2018
1 Read

Homozygous DMRT2 variant associates with severe rib malformations in a newborn.

Am J Med Genet A 2018 May;176(5):1216-1221

Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.

Spondylocostal dysostosis (SCD) is a rare disorder characterized by vertebral segmentation defects and malformations of the ribs. SCD patients have some degree of (kypho)scoliosis, short stature and suffer from respiratory impairment due to the reduced size of their thoracic cage. Mutations in DLL3, MESP2, LFNG, HES7, TBX6, and RIPPLY2 are known to cause different subtypes of SCD. Read More

View Article
May 2018
1 Read

A patient with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and severe hypoganglionosis associated with a novel SOX10 mutation.

Am J Med Genet A 2018 May;176(5):1195-1199

Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.

In this report, we present the case of a female infant with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH) associated with a novel frameshift mutation (c.842dupT) in exon 5, the last exon of SOX10. She had severe hypoganglionosis in the small intestine and entire colon, and suffered from frequent enterocolitis. Read More

View Article

Bohring-Opitz syndrome caused by an ASXL1 mutation inherited from a germline mosaic mother.

Am J Med Genet A 2018 May;176(5):1249-1252

Roberts Individualized Medical Genetics Center, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Bohring-Opitz syndrome (BOS) is characterized clinically by severe developmental delays, microcephaly, failure to thrive, and characteristic facial features (prominent eyes, facial nevus simplex [flammeus], and others). Most patients meeting the clinical criteria for BOS (MIM: 605039) have a de novo nonsense or frameshift variant in ASXL1. We report a case of BOS caused by a pathogenic ASXL1 variant inherited from a germline mosaic mother. Read More

View Article

2016 Children's Tumor Foundation conference on neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis.

Am J Med Genet A 2018 May;176(5):1258-1269

Hereditary Cancer Group, The Institute for Health Science Research Germans Trias i Pujol (IGTP)-PMPPC, Barcelona, Spain.

Organized and hosted by the Children's Tumor Foundation (CTF), the Neurofibromatosis (NF) conference is the premier annual gathering for clinicians and researchers interested in neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). The 2016 edition constituted a blend of clinical and basic aspects of NF research that helped in clarifying different advances in the field. The incorporation of next generation sequencing is changing the way genetic diagnostics is performed for NF and related disorders, providing solutions to problems like genetic heterogeneity, overlapping clinical manifestations, or the presence of mosaicism. Read More

View Article
May 2018
2 Reads

The Society for Craniofacial Genetics and Developmental Biology 40th annual meeting.

Am J Med Genet A 2018 May;176(5):1270-1273

Orthopaedic Trauma Institute, Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California.

View Article