Publicaties
Gekozen filters:
Gekozen filters:
Missense mutations in inositol 1,4,5-trisphosphate receptor type 3 result in leaky Ca2+ channels and activation of store-operated Ca2+ entry KU Leuven
Mutations in all subtypes of the inositol 1,4,5-trisphosphate receptor Ca2+ release channel are associated with human diseases. In this report, we investigated the functionality of three neuropathy-associated missense mutations in IP3R3 (V615M, T1424M, and R2524C). The mutants only exhibited function when highly over-expressed compared to endogenous hIP3R3. All variants resulted in elevated basal cytosolic Ca2+ levels, decreased endoplasmic ...
Cancer predisposing missense and protein truncating BARD1 mutations in non BRCA1 or BRCA2 breast cancer families Vrije Universiteit Brussel
Fifteen years ago BRCA1 and BRCA2 were reported as high penetrant breast cancer predisposing genes. However, mutations in these genes are found in only a fraction of high risk families. BARD1 is a candidate breast cancer gene, but only a limited number of missense mutations with rather unclear pathogenic consequences have been reported.We screened 196 high risk breast cancer families for the occurrence of BARD1 variants. All genetic variants ...
COMMON VARIABLE IMMUNODEFICIENCY CAUSED BY A HOMOZYGOUS MISSENSE MUTATION IN TRNT1 KU Leuven
We identified a 23-year old male patient with mental retardation, dysmorphic features, bilateral cataract, Crohn’s disease, and low levels of IgG, IgA, IgM. He was classified as having common variable immunodeficiency and has been treated with immunoglobulin substitution since the age of 12 months. Initially, the total lymphocyte count, B- and NK-cell numbers were normal but dropped significantly after age 21. Whole exome sequencing identified a ...
Reduced secretion and altered proteolytic processing caused by missense mutations in progranulin Universiteit Antwerpen
Progranulin (GRN) is a secreted growth factor involved in various cellular functions, and loss-of-function mutations are a major cause of frontotemporal lobar degeneration (FTLD) with TDP-43 positive pathology. Most FTLD-related GRN mutations are nonsense mutations resulting in reduced GRN expression. Nonsynonymous GRN missense mutations have been described as risk factor for neurodegenerative brain diseases, but their pathogenic nature remains ...
Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance Universiteit Antwerpen
Objective In this study, we hypothesized that mutations in the resistin encoding gene, RETN, may cause a monogenic form of obesity. Design/methods We screened the coding region of RETN in 81 morbidly obese adults, 263 overweight and obese children/adolescents, and 116 healthy lean subjects. In vitro experiments include qPCR, ELISA, and western blot for WT and mutant resistin transfected into 3T3-L1 adipocytes. Results Mutation analysis ...
Homozygous missense STRADA mutation in a patient with polyhydramnios, megalencephaly and symptomatic epilepsy syndrome KU Leuven
Homozygous or compound heterozygous mutations in STRADA cause polyhydramnios, megalencephaly and symptomatic epilepsy syndrome (PMSE), with additional features of distinctive facial traits and severe developmental delay or intellectual disability. This syndrome was first defined in 16 Old Order Mennonite patients, carrying a homozygous STRADA deletion of exon 9-13. Five additional PMSE patients have been reported since, each of them with ...
Severe ALG8-CDG (CDG-Ih) associated with homozygosity for two novel missense mutations detected by exome sequencing of candidate genes KU Leuven
Posttranslationally glycosylated proteins are important in many biological processes in humans and congenital defects of glycosylation (CDGs) are associated with a broad range of phenotypes. Type I CDGs are a group of rare autosomal recessive conditions. To date 17 subtypes have been enzymatically and molecularly characterized. Impaired function of the enzyme dolichyl pyrophosphate Glc(1)Man(9)GlcNAc(2) alpha-1,3-glucosyltransferase encoded by ...
Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome KU Leuven
Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exomes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening identified nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations were confirmed to be de novo when parental samples were ...
Characterization of the c.190T > C missense mutation in BRCA1 codon 64 (Cys64Arg) Universiteit Gent
In the Milan area (Northern Italy), we identified a family characterized by a high prevalence of ovarian and breast cancer cases (5 out of 6 subjects, over 3 generations), and a predominant prevalence of ovarian lesions (4 out of 5 patients). Analysis of BRCA1 and BRCA2 genes allowed the identification of the missense c.190T>C mutation in codon 64 (Cys64Arg) of BRCA1. The aims of the present investigation were to characterize the functional ...