Identification of a novel WFS1 homozygous nonsense mutation in Jordanian children with Wolfram syndrome.
Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder characterized by the presentation of early onset type I diabetes mellitus and optic atrophy with later onset diabetes insipidus and deafness. WFS1 gene was identified on chromosome 4p16.1 as the gene responsible for WS disease given that most of the WS patients were found to carry mutations in this gene. This study was carried out to investigate the molecular spectrum of WFS1 gene in Jordanian families. Molecular and clinical characterization was performed on five WS patients from two unrelated Jordanian families. Our data indicated that WS patients of the first family harbored two deletion mutations (V415del and F247fs) located in exon 8 and exon 7 respectively, with a compound heterozygous pattern of inheritance; while in the second family, we identified a novel nonsense mutation (W185X) located in exon 5 in the N-terminal cytoplasmic domain with a homozygous pattern of inheritance. This mutation can be considered as loss of function mutation since the resulting truncated protein lost both the transmembrane domain and the C-terminal domain. Additionally, the W185X mutation lies within the CaM binding domain in wolframin protein which is thought to have a role in the regulation of wolframin function in response to calcium levels.
Department of Applied Biology, Faculty of Science, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Khaldon
K
Bodoor
Department of Applied Biology, Faculty of Science, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
Osama
O
Batiha
Faculty of Medicine, Yarmouk University, Irbid, Jordan.
Ayman
A
Abu-Awad
Department of Internal Medicine, King Hussein Medical Center, Amman, Jordan.
Khaldon
K
Al-Sarihin
Department of Applied Biology, Faculty of Science, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
Haya
H
Ziad
Department of Applied Biology, Faculty of Science, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
Yousef
Y
Jarun
Department of Applied Biology, Faculty of Science, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
Aya
A
Abu-Sheikha
Department of Applied Biology, Faculty of Science, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
Sara
S
Abu Jalboush
Princess Iman Center, King Hussein Medical Center, Amman, Jordan.
Khoulod S
KS
Alibrahim
Compound heterozygosity; Novel mutation; WFS1; Wolfram syndrome; Wolframin