title: RECURRENT RAB3GAP1 MUTATIONS IN THE TURKISH POPULATION.
abstract: Warburg Micro Syndrome (WARBM, MIM 600118) is a rare, severe autosomal recessive neurodevelopmental disorder characterized by microcephaly, microphthalmia, microcornea, congenital cataract, cortical dysplasia, corpus callosum hypoplasia, intellectual disability, hypotonia and hypogonadism. RABS, small G proteins belonging to the RAS superfamily, are master regulators of vesicle trafficking in the cell. The identification of mutations in the RAB3GAP1 and RAB3GAP2 genes, which together encode the RAB3GTPase-activating protein, a key regulator in calcium-mediated exocytosis of neurotransmitters and hormones, has underpinned abnormal development of the brain, eye and genitalia as cardinal features of this syndrome. More than 100 patients have been reported with WARBM, with mutations in the RABGAP1, RABGAP2, RAB18 and TBC1D20 genes. The objective of the study was to describe the recurrent RAB3GAP1 mutations and compare the clinical features of the patients with WARBM in the Turkish population. Here we report two brothers with Warburg Micro Syndrome 1 from a non-consanguineous Turkish family with clinical features similar to those previously reported in Turkish patients with RAB3GAP1 mutations. We found that the c.748+1G>A splice-site mutation in RAB3GAP1 intron 8 is common and has so far only been detected in patients of Turkish ethnic origin. Although one of our patients has a distal extra crease on the 4th finger and another has nephrolithiasis, there does not appear to be any specific phenotypic findings associated with this mutation.
authors: S
authors: S
authors: Tasdemir
authors: I
authors: I
authors: Sahin
authors: D J
authors: DJ
authors: Morris-Rosendahl
authors: E
authors: E
authors: Marzioglu
authors: A
authors: A
authors: Cayir
authors: I
authors: I
authors: Yuce
authors: A
authors: A
authors: Tatar
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002386:Cataract / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D003315:Cornea / Q000002:abnormalities*; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis* / Q000235:genetics*; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D009896:Optic Atrophy / Q000175:diagnosis* / Q000235:genetics*; D014421:Turkey; D020692:rab3 GTP-Binding Proteins / Q000235:genetics*
chemical_list: D020692:rab3 GTP-Binding Proteins