Novel complex Re-Arrangement of ARG1 commonly shared by unrelated patients with Hyperargininemia

Hyperargininemia is a very rare progressive neurometabolic disorder caused by deficiency of hepatic cytosolic arginase I, resulting from mutations in the ARG1 gene. Until now, some mutations were reported worldwide and none of them were of Southeast Asian origins. Furthermore, most reported mutation...

Full description

Saved in:
Bibliographic Details
Published in:Gene 2014-01, Vol.533 (1), p.240-245
Main Authors: Mohseni, Jafar, Boon Hock, Chia, Abdul Razak, Che, Othman, Syah Nor Iman, Hayati, Fatemeh, PeiTee, Winnie Ong, Haniffa, Muzhirah, Zilfalil, Bin Alwi, Mohd. Rawi, Rowani, Ngu, Lock-Hock, Sasongko, Teguh Haryo
Format: Article
Language:English
Subjects:
ARG1
Arginase - genetics
Arginase deficiency
Base Sequence
Child
Child, Preschool
Complex re-arrangement
DNA
Female
Gene Rearrangement
Humans
Hyperargininemia
Hyperargininemia - genetics
Infant
Malaysia
Male
Molecular Sequence Data
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Sequence Homology, Nucleic Acid
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hyperargininemia is a very rare progressive neurometabolic disorder caused by deficiency of hepatic cytosolic arginase I, resulting from mutations in the ARG1 gene. Until now, some mutations were reported worldwide and none of them were of Southeast Asian origins. Furthermore, most reported mutations were point mutations and a few others deletions or insertions. This study aims at identifying the disease-causing mutation in the ARG1 gene of Malaysian patients with hyperargininemia. We employed a series of PCR amplifications and direct sequencing in order to identify the mutation. We subsequently used quantitative real-time PCR to determine the copy number of the exons flanking the mutation. We blasted our sequencing data with that of the reference sequence in the NCBI in order to obtain positional insights of the mutation. We found a novel complex re-arrangement involving insertion, inversion and gross deletion of ARG1 (designated g.insIVS1+1899GTTTTATCAT;g.invIVS1+1933_+1953;g.delIVS1+1954_IVS2+914;c.del116_188;p.Pro20SerfsX4) commonly shared by 5 patients with hyperargininemia, each originating from different family. None of the affected families share known relationship with each other, although four of the five patients were known to have first-cousin consanguineous parents. This is the first report of complex re-arrangement in the ARG1. Further analyses showing that the patients have shared the same geographic origin within the northeastern part of Malaysia prompted us to suggest a simple molecular screening of hyperargininemia within related ethnicities using a long-range PCR. •First report of complex re-arrangement mutation in ARG1 gene.•First report of ARG1 mutation among Hyperargininemia patients of South-East Asian.•The mutation was found to be common in un-related patients with Hyperargininemia.•The finding led to simple screening method for the disorder among similar ethnicities.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2013.09.081