The novel compound heterozygous mutations, V434del and W666X, in WFS1 gene causing the Wolfram syndrome in a Chinese family

Abstract

Wolfram syndrome (WFS), also known as DIDMOAD, is an infrequent cause of diabetes mellitus. WFS is an autosomal recessive neurodegenerative disease characterized by various clinical manifestations such as diabetes mellitus, optic atrophy, diabetes insipidus, deafness, neurological symptoms, renal tract abnormalities, psychiatric disorders, and gonadal disorders. The majority of patients with WFS carry the loss of function mutations in the WFS1 gene. The exons 2-8 of the WFS1 gene from one Chinese WFS patient were amplified by the polymerase chain reaction (PCR), subcloning techniques and direct sequence determination was applied to the amplified fragments. The compound heterozygous mutation of a 3-bp (GAC) deletion (V434del) and another compound heterozygous mutation (G-->N)(W666X) in exon 8 of WFS1 gene was identified in the patient. Other seventeen members of her family were investigated. Four cases with heterozygotes had been found through screening for the mutation V434del and five cases for the mutation W666X in the whole family. This is the first report of WFS with the mutation V434del and W666X in the WFS1 gene.

Wolfram syndrome in the Polish population: novel mutations and genotype-phenotype correlation

“…This wide tissue distribution of wolframin presumably contributes to the pleiotropic effects of mutation of WFS1 . Currently, about 130 mutations resulting in Wolfram syndrome have been described, and most of them are inactivating 6–12 . The list of described mutations is expected to grow as previously untested populations are studied.…”

“…Currently, about 130 mutations resulting in Wolfram syndrome have been described, and most of them are inactivating. [6][7][8][9][10][11][12] The list of described mutations is expected to grow as previously untested populations are studied.…”

WS1 gene mutation analysis of Wolfram syndrome in a Chinese patient and a systematic review of literatures

“…A total of 219 patients were included in the 24 articles with full text [4,6,. Clinical characters were described in 211 patients and WFS1 mutations were described in 218 patients.…”

“…Thirteen primers were designed and generated by Invitrogen (USA) to amplify the open reading frame (ORF) of WS1 gene (NM_006005) as previously reported [6]. PCR was performed with Advantage-GC Genomic Polymerase Mix (Clontech, USA) in ABI PCR amplifier 9700 (Applied Biosystems, USA).…”

Detecting Low Frequent Loss-of-Function Alleles in Genome Wide Association Studies with Red Hair Color as Example

“…Some examples are HFE and hemochromatosis [7], PLA2G7 and coronary heart diseases [8], SLC22A12/SLC2A9 and renal hypouricemia [9], [10], KCNQ1 and Jervell and Lange-Nielsen syndrome [11], NCCT and Gitelmańs syndrome [12], ABCC6/ GGCX and pseudoxanthoma elasticum [13], [14], [15], TG and congenital goiter [16], SCN5A and Brugada syndrome [17], P2RX7 and inflammatory response [18], ABCA12 and congenital ichthyoses [19], TRIM32 and nephrogenic diabetes insipidus [20], WFS1 and Wolfram syndrome [21], and CLDN16 and hypomagnesaemia [22]. Through this study we use LOF variants in MC1R and red hair color as an example where empirical data were available.…”