Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A novel de novo RNF216 mutation associated with autosomal recessive Huntington-like disorder.

ABSTRACT: Mutations in RNF216 have been found to be associated with autosomal recessive Huntington-like disorder. Here, we describe a patient with Huntington-like disorder caused by a novel de novo RNF216 mutation. The patient started to have choreatic movements of both hands, slowly progressing to head, face, and four extremities, with prominent cognitive deterioration. White matter lesions in cerebral hemispheres and brainstem, cerebellar atrophy, and low gonadotropin serum levels have been demonstrated. We have identified a homozygous deletion of exon 2 in the RNF216 gene by whole-exome sequencing. Our findings increased genetic knowledge of autosomal recessive Huntington-like disorder and extended the ethnic distribution of RNF216 mutations.

SUBMITTER: Chen KL

PROVIDER: S-EPMC7261743 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A novel de novo RNF216 mutation associated with autosomal recessive Huntington-like disorder.

Chen Ke-Liang KL Zhao Gui-Xian GX Wang He H Wei Lei L Huang Yu-Yuan YY Chen Shi-Dong SD Lin Bi-Ying BY Dong Qiang Q Cui Mei M Yu Jin-Tai JT

Annals of clinical and translational neurology 20200502 5

Mutations in RNF216 have been found to be associated with autosomal recessive Huntington-like disorder. Here, we describe a patient with Huntington-like disorder caused by a novel de novo RNF216 mutation. The patient started to have choreatic movements of both hands, slowly progressing to head, face, and four extremities, with prominent cognitive deterioration. White matter lesions in cerebral hemispheres and brainstem, cerebellar atrophy, and low gonadotropin serum levels have been demonstrated ...[more]

PMID: 32358900

Similar Datasets

Localization of the gene for a novel autosomal recessive neurodegenerative Huntington-like disorder to 4p15.3.

Project description:A consanguineous family affected by an autosomal recessive, progressive neurodegenerative Huntington-like disorder, was tested to rule out juvenile-onset Huntington disease (JHD). The disease manifests at approximately 3-4 years and is characterized by both pyramidal and extrapyramidal abnormalities, including chorea, dystonia, ataxia, gait instability, spasticity, seizures, mutism, and intellectual impairment. Brain magnetic resonance imaging (MRI) findings include progressive frontal cortical atrophy and bilateral caudate atrophy. Huntington CAG trinucleotide-repeat analyses ruled out JHD, since all affected individuals had repeat numbers within the normal range. The presence of only four recombinant events (straight theta=.2) between the disease and the Huntington locus in 20 informative meioses suggested that the disease localized to chromosome 4. Linkage was initially achieved with marker D4S2366 at 4p15.3 (LOD 3.03). High-density mapping at the linked locus resulted in homozygosity for markers D4S431 and D4S394, which span a 3-cM region. A maximum LOD score of 4.71 in the homozygous interval was obtained. Heterozygosity at the distal D4S2366 and proximal D4S2983 markers defines the maximum localization interval (7 cM). Multiple brain-related expressed sequence tags (ESTs) with no known disease association exist in the linkage interval. Among the three known genes residing in the linked interval (ACOX3, DRD5, QDPR), the most likely candidate, DRD5, encoding the dopamine receptor D5, was excluded, since all five affected family members were heterozygous for an intragenic dinucleotide repeat. The inheritance pattern and unique localization to 4p15.3 are consistent with the identification of a novel, autosomal recessive, neurodegenerative Huntington-like disorder.

| S-EPMC1288097 | biostudies-literature

Novel REEP6 gene mutation associated with autosomal recessive retinitis pigmentosa.

Project description:PurposeThis study reports the ophthalmic and genetic findings of a Cameroonian patient with autosomal recessive retinitis pigmentosa (arRP) caused by a novel Receptor Expression Enhancing Protein 6 (REEP6) homozygous mutation.Patient and methodsA 33-year-old man underwent comprehensive ophthalmic examinations, including visual acuity measurements, dilated fundus imaging, electroretinography (ERG), and spectral-domain optical coherence tomography (SD-OCT). Short-wavelength fundus autofluorescence (SW-AF) and near-infrared fundus autofluorescence (NIR-AF) were also evaluated. Whole exome sequencing (WES) was used to identify potential pathogenic variants.ResultsFundus examination revealed typical RP findings with additional temporal ten micron yellow dots. SD-OCT imaging revealed cystoid macular edema and perifoveal outer retinal atrophy with centrally preserved inner segment ellipsoid zone (EZ) bands. Hyperreflective spots were seen in the inner retinal layers. On SW-AF images, a hypoautofluorescent area in the perifoveal area was observed. NIR-AF imaging revealed an irregularly shaped hyperautofluorescent ring. His visual acuity was mildly affected. ERG showed undetectable rod responses and intact cone responses. Genetic testing via WES revealed a novel homozygous mutation (c.295G>A, p.Glu99Lys) in the gene encoding REEP6, which is predicted to alter the charge in the transmembrane helix.ConclusionsThis report is not only the first description of a Cameroonian patient with arRP associated with a REEP6 mutation, but also this particular genetic alteration. Substitution of p.Glu99Lys in REEP6 likely disrupts the interactions between REEP6 and the ER membrane. NIR-AF imaging may be particularly useful for assessing functional photoreceptor cells and show an "avocado" pattern of hyperautofluorescence in patients with the REEP6 mutation.

| S-EPMC7310602 | biostudies-literature

Case report: A novel <i>de novo</i> deletion mutation of <i>DYRK1A</i> is associated with intellectual developmental disorder, autosomal dominant 7.

Project description:BackgroundIntellectual developmental disorder 7 (also named DYRK1A syndrome) is an autosomal dominant disease. The main clinical features of DYRK1A syndrome include intellectual disability, microcephaly, and developmental delay. This study aimed to identify pathogenic variants in a Chinese girl with developmental delay, impaired social interaction, and autistic behavior.Case presentationThe case was a 6-year-old girl. Clinical symptoms of the patient mainly included developmental delay, seizures, autistic behavior and impaired social interaction. The patient presented with microcephaly, bushy eyebrows, a short lingual frenum, binocular esotropia, bilateral valgus and external rotation, and walked with an abnormal gait. Using whole-exome sequencing, we identified a 9,424 bp de novo heterozygous deletion (containing coding exons 10, 11, and 12, and partial sequences of non-coding exon 12) in DYRK1A, which is responsible for DYRK1A syndrome. The DYRK1A variant is classified as pathogenic according to the criteria of the American College of Medical Genetics and Genomics.ConclusionsThe findings of this study augment the data regarding the pathogenic variants of DYRK1A and provide important information for molecular diagnosis.

| S-EPMC10235440 | biostudies-literature

A Novel de novo FZD2 Mutation in a Patient with Autosomal Dominant Omodysplasia.

Project description:We described a heterozygous de novo mutation (G434V) in the frizzled class receptor 2 (FZD2) gene in a patient with distinct facial features including hypertelorism, bilateral cleft lip/palate, short nose with a broad nasal bridge, microretrognathia, and bilateral shortness of the upper limbs, first metacarpal bones, and middle phalanges of the 5th digits. The findings of our patient were compared to an autosomal dominant omodysplasia (OMOD2) family with FZD2 mutation reported in the literature. OMOD2 is a rare skeletal dysplasia and characterized by facial dysmorphism and shortness of the upper extremities and first metacarpal bones. This is the second report which supports the findings of the first family described and points out that heterozygous FZD2 mutations may be disease-causing for OMOD2.

| S-EPMC5701278 | biostudies-literature

Novel ITGB6 mutation in autosomal recessive amelogenesis imperfecta.

Project description:Hereditary defects in tooth enamel formation, amelogenesis imperfecta (AI), can be non-syndromic or syndromic phenotype. Integrins are signaling proteins that mediate cell-cell and cell-extracellular matrix communication, and their involvement in tooth development is well known. The purposes of this study were to identify genetic cause of an AI family and molecular pathogenesis underlying defective enamel formation.We recruited a Turkish family with isolated AI and performed mutational analyses to clarify the underlying molecular genetic etiology.Autozygosity mapping and exome sequencing identified a novel homozygous ITGB6 transversion mutation in exon 4 (c.517G>C, p.Gly173Arg). The glycine at this position in the middle of the ?I-domain is conserved among a wide range of vertebrate orthologs and human paralogs. Clinically, the enamel was generally thin and pitted with pigmentation. Thicker enamel was noted at the cervical area of the molars.In this study, we identified a novel homozygous ITGB6 mutation causing isolated AI, and this advances the understanding of normal and pathologic enamel development.

| S-EPMC4440386 | biostudies-literature

Genomic duplication in Dyggve Melchior Clausen syndrome, a novel mutation mechanism in an autosomal recessive disorder.

Project description:BackgroundDyggve Melchior Clausen syndrome (DMC) is a severe autosomal recessive skeletal dysplasia associated with mental retardation. Direct sequencing of genomic DNA has identified causative mutations in the gene Dymeclin (chromosome 18q12-21), with the majority predicting the generation of a truncated protein product.ObjectiveTo carry out molecular genetic studies in three DMC kindreds.ResultsTwo novel nonsense mutations and two complex genomic duplication events resulting in exon repetition were identified.ConclusionsExon dosage assessment or mRNA analysis, in addition to direct genomic DNA sequencing, should be employed in the investigation of DMC affected individuals. Genomic duplication may be the causative mutation mechanism in other autosomal recessive disorders.

| S-EPMC1735964 | biostudies-literature

Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder

Project description:Intellectual disability (ID) is a highly heterogeneous disorder with hundreds of associated genes. Despite progress in the identification of the genetic causes of ID following the introduction of high-throughput sequencing, about half of affected individuals still remain without a molecular diagnosis. Consanguineous families with affected individuals provide a unique opportunity to identify novel recessive causative genes. In this report, we describe a novel autosomal recessive neurodevelopmental disorder. We identified two consanguineous families with homozygous variants predicted to alter the splicing of ATP9A which encodes a transmembrane lipid flippase of the class II P4-ATPases. The three individuals homozygous for these putatively truncating variants presented with severe ID, motor and speech impairment, and behavioral anomalies. Consistent with a causative role of ATP9A in these patients, a previously described Atp9a−/− mouse model showed behavioral changes.

| S-EPMC8586153 | biostudies-literature

SIGMAR1 mutation associated with autosomal recessive Silver-like syndrome.

Project description:ObjectiveTo describe the genetic and clinical features of a simplex patient with distal hereditary motor neuropathy (dHMN) and lower limb spasticity (Silver-like syndrome) due to a mutation in the sigma nonopioid intracellular receptor-1 gene (SIGMAR1) and review the phenotypic spectrum of mutations in this gene.MethodsWe used whole-exome sequencing to investigate the proband. The variants of interest were investigated for segregation in the family using Sanger sequencing. Subsequently, a larger cohort of 16 unrelated dHMN patients was specifically screened for SIGMAR1 mutations.ResultsIn the proband, we identified a homozygous missense variant (c.194T>A, p.Leu65Gln) in exon 2 of SIGMAR1 as the probable causative mutation. Pathogenicity is supported by evolutionary conservation, in silico analyses, and the strong phenotypic similarities with previously reported cases carrying coding sequence mutations in SIGMAR1. No other mutations were identified in 16 additional patients with dHMN.ConclusionsWe suggest that coding sequence mutations in SIGMAR1 present clinically with a combination of dHMN and pyramidal tract signs, with or without spasticity, in the lower limbs. Preferential involvement of extensor muscles of the upper limbs may be a distinctive feature of the disease. These observations should be confirmed in future studies.

| S-EPMC5067545 | biostudies-literature

A de novo mutation in PRICKLE1 associated with myoclonic epilepsy and autism spectrum disorder.

Project description:Homozygous recessive mutations in the PRICKLE1 gene were first described in three consanguineous families with myoclonic epilepsy. Subsequent studies have identified neurological abnormalities in humans and animal models with both heterozygous and homozygous mutations in PRICKLE1 orthologs. We describe a 7-year-old with a novel de novo missense mutation in PRICKLE1 associated with epilepsy, autism spectrum disorder and global developmental delay.

| S-EPMC6251753 | biostudies-literature

A Novel de novo Mutation in CEACAM16 Associated with Postlingual Hearing Impairment.

Project description:Mutations in CEACAM16 cause autosomal dominant nonsyndromic hearing loss (DFNA4B). So far, 2 families have been reported with segregating missense mutations, both in the immunoglobulin constant domain A of the CEACAM16 protein. In this study, we used the TruSight One panel to investigate a parent-child trio without familial history of hearing loss and one affected child. When filtering for recessive inheritance and de novo events, we discovered a de novo CEACAM16 mutation (c.1094T>G, p.Leu365Arg) as the sole likely pathogenic variant. The de novo mutation was confirmed by Sanger sequencing and STR analysis. The proband's hearing loss closely matches the described onset and severity for DFNA4B. We present the third CEACAM16 variant and the first de novo mutation in CEACAM16. This de novo mutation is robustly described as a pathogenic mutation according to in silico mutation prediction tools and affects a highly conserved amino acid in the most strongly conserved CEACAM16 N2 domain. Our strategy of screening family trios enhances de novo mutation discovery and the exclusion of other variants of potential interest through pedigree filtering.

| S-EPMC4662267 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data