98%
921
2 minutes
20
NALCN channelosome complex contributes to maintaining resting membrane potential. The complex has four domains including two intracellular domains (UNC79 and UNC80), one transmembrane domain (NALCN) and one extracellular domain (FAM155A). Mutations in UNC80 were previously linked to infantile hypotonia with psychomotor retardation and characteristics facies 2. A 6-year-old male with neurodevelopmental disorder was referred for clinical exome sequencing. Sanger sequencing was conducted for variant confirmation and segregation analysis. The index had severe to profound neurodevelopmental delay, progressive failure to thrive, severe constipation and reflux, and sociable skills. Trio exome sequencing identified a homozygous c.6495G > A change causing p.Trp2165Ter in UNC80 in the proband. The variant was novel and predicted to be deleterious. We reported a novel nonsense mutation in UNC80. Our case also established the association between, and sociable skills and severe gastrointestinal problems.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/ajmg.a.63213 | DOI Listing |
NAR Mol Med
April 2025
Tumor Vaccine and Biotechnology Branch, Division of Cellular Therapy 2, Office of Cellular Therapy and Human Tissue, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, United States.
Changes in global climate have contributed to increased tick and mosquito (vector) populations and subsequent vector-borne flavivirus infections in humans. This increase poses a threat to the safety of human-derived biologics such as cell and gene therapy. We conducted time-course transcriptomic and protein analyses to uncover host molecular factors driving the virulence of Zika virus (ZIKV) and Dengue virus (DENV) in relation to host defense mechanisms, as these viruses have caused recent flavivirus outbreaks.
View Article and Find Full Text PDFBackground Over 300 mutations in have been identified as causes of early-onset Alzheimer's disease (EOAD). While these include missense mutations and a few insertions, deletions, or duplications, none result in open reading frame shifts, and all alter γ-secretase function to increase the long/short Aβ ratio. Methods We identified a novel heterozygous nonsense variant, c.
View Article and Find Full Text PDFJ Equine Vet Sci
September 2025
Genetic Analysis Department, Laboratory of Racing Chemistry, 1731-2 Tsurutamachi, Utsunomiya, Tochigi 320-0851, Japan.
Background: Thoroughbreds have been maintained as a closed breed for over 300 years since the crossbreeding between Arabian stallions and English mares. Despite interest in germline de novo mutations across species, their frequency in horses, particularly in Thoroughbreds, remains largely unexplored.
Aims/objective: This study aimed to identify de novo mutations in Thoroughbreds and estimate their frequency within a genetically closed population.
Ophthalmic Genet
September 2025
Department of Ophthalmology, American University of Beirut Medical Center, Beirut, Lebanon.
Background: Retinoblastoma is the most common intraocular tumor of childhood. In Lebanon, its incidence is reported at 3.6 per million person-years.
View Article and Find Full Text PDFMol Genet Metab
August 2025
Department of Molecular and Human Genetics, Baylor Coll. of Medicine, Houston, TX, United States; Texas Children's Hospital, Houston, TX, United States; Baylor Genetics, Houston, TX, United States; Joint BCM-CUHK Center of Medical Genetics, Prince of Wales Hospital, ShaTin, Hong Kong, China. Electro
Triosephosphate isomerase (TPI) is a ubiquitously expressed enzyme encoded by the TPI1 gene. It catalyzes the interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate in the fifth step of glycolysis. TPI deficiency (TPI Df; MIM# 615512) is an autosomal recessive disorder due to biallelic pathogenic variants in TPI1.
View Article and Find Full Text PDF