Project description:Presented here are five members of a family that was ascertained from an isolated, consanguineous, indigenous Amerindian community in Colombia that was affected with calpain 3-related, limb-girdle muscular dystrophy type R1. These patients are homozygous for a unique and novel deletion of four bases (TGCC) in exon 3 of the calpain 3 gene (CAPN3) (NM_000070.2; NP_000061.1) (g.409_412del). The mutation site occurs at the CysPc protein domain, triggering a modified truncated protein structure and affecting motifs within the calpain-like thiol protease family (peptidase family C2) region. The patients reported here developed a very severe phenotype with primary contractures, spinal rigidity in the early stages of the disease, and bilateral talipes equinovarus (clubfoot) in the most affected patients who had the selective involvement of their extremities' distal muscles in a way that resembled Emery-Dreifuss syndrome. We recommend mandatory screening for calpainopathy in all patients with an Emery-Dreifuss-like syndrome or those presenting a non-congenital illness with primary contractures and who, because of other data, are suspected of having muscular dystrophy.

| S-EPMC7074289 | biostudies-literature

Unusual electrocardiographic presentation associated with severe hyperkalemia.

Project description: Not available

| S-EPMC10108882 | biostudies-literature

A nonsense mutation in the IKBKG gene in mares with incontinentia pigmenti.

Project description:Ectodermal dysplasias (EDs) are a large and heterogeneous group of hereditary disorders characterized by abnormalities in structures of ectodermal origin. Incontinentia pigmenti (IP) is an ED characterized by skin lesions evolving over time, as well as dental, nail, and ocular abnormalities. Due to X-linked dominant inheritance IP symptoms can only be seen in female individuals while affected males die during development in utero. We observed a family of horses, in which several mares developed signs of a skin disorder reminiscent of human IP. Cutaneous manifestations in affected horses included the development of pruritic, exudative lesions soon after birth. These developed into wart-like lesions and areas of alopecia with occasional wooly hair re-growth. Affected horses also had streaks of darker and lighter coat coloration from birth. The observation that only females were affected together with a high number of spontaneous abortions suggested an X-linked dominant mechanism of transmission. Using next generation sequencing we sequenced the whole genome of one affected mare. We analyzed the sequence data for non-synonymous variants in candidate genes and found a heterozygous nonsense variant in the X-chromosomal IKBKG gene (c.184C>T; p.Arg62*). Mutations in IKBKG were previously reported to cause IP in humans and the homologous p.Arg62* variant has already been observed in a human IP patient. The comparative data thus strongly suggest that this is also the causative variant for the observed IP in horses. To our knowledge this is the first large animal model for IP.

| S-EPMC3852476 | biostudies-literature

IKBKG (NEMO) 5' Untranslated Splice Mutations Lead to Severe, Chronic Disseminated Mycobacterial Infections.

Project description:Four patients with adult-onset, disseminated mycobacterial infection had 5' UTR mutations in IKBKG without clear physical stigmata of NEMO deficiency. These mutations caused decreased levels of NEMO protein and Toll-like receptor driven cytokine production. Three patients died from disseminated disease. These mutations may be missed by whole exome sequencing.

| S-EPMC6051446 | biostudies-literature

Atypical clinical presentation of a WT1-related syndrome associated with a novel exon 6 gene mutation.

Project description:Wilms' tumour suppressor gene-1 (WT1) plays a critical role in kidney development and function. Several WT1 mutations can occur in exons 7, 8 and 9 and they have been associated with Denys-Drash syndrome. WT1 mutations of intron 9 have been reported too and associated with Frasier syndrome. However, overlapping and incomplete forms of both the syndromes have been described. We report a novel sequence variant (c.1012A>T) of the WT1 gene in exon 6 (p.R338X) in a 18-year-old girl with a history of Wilms' tumour, minor gonadal changes and relatively late-onset nephropathy. WT1-related nephropathies should be suspected in every patient with proteinuria not associated to immunological changes when a congenital neoplasia or minor gonadal anomalies are present.

| S-EPMC3669930 | biostudies-literature

PLA2G6 -Associated Neurodegeneration: Report of a Novel Mutation in Two Siblings with Strikingly Different Clinical Presentation.

Project description: Not available

| S-EPMC6353338 | biostudies-literature

A mutation of Ikbkg causes immune deficiency without impairing degradation of IkappaB alpha.

Project description:Null alleles of the gene encoding NEMO (NF-kappaB essential modulator) are lethal in hemizygous mice and men, whereas hypomorphic alleles typically cause a syndrome of immune deficiency and ectodermal dysplasia. Here we describe an allele of Ikbkg in mice that impaired Toll-like receptor signaling, lymph node formation, development of memory and regulatory T cells, and Ig production, but did not cause ectodermal dysplasia. Degradation of IkappaB alpha, which is considered a primary requirement for NEMO-mediated immune signaling, occurred normally in response to Toll-like receptor stimulation, yet ERK phosphorylation and NF-kappaB p65 nuclear translocation were severely impaired. This selective loss of function highlights the immunological importance of NEMO-regulated pathways beyond IkappaB alpha degradation, and offers a biochemical explanation for rare immune deficiencies in man.

| S-EPMC2840324 | biostudies-literature

Project description:BackgroundA highly variable phenotype characterized by thyroid, respiratory and neurological defects has been reported in an already established group of disorders namely NKX2.1-related disorders. We describe here the case of an infant with a novel mutation of the NKX2.1 gene characterized by mild clinical presentation. Aim of the study was to elucidate the genotype-phenotype correlation in our patient.MethodsWe performed genetic analysis of the NKX2.1 gene in an infant with no neonatal respiratory distress and near-normal results at neonatal screening test for congenital hypothyroidism, choreoathetosis, ataxia and delayed independent walking.ResultsA novel mutation of the NKX2.1 gene has been identified, that is responsible for a mild framework of congenital hypothyroidism and neurological symptoms.ConclusionsThe frequency of congenital hypothyroidism cases associated with NKX2.1 mutations is expected to be higher in a subgroup of patients, selected according to the neurological presentation. In these patients the analysis of NKX2.1 mutational status is recommended.

| S-EPMC4477322 | 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