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Glycogen storage disease type IIIa: first report of a causative missense mutation (G1448R) of the glycogen debranching enzyme gene found in a homozygous patient
Author(s) -
Okubo Minoru,
Kanda Fumio,
Horinishi Asako,
Takahashi Keiichi,
Okuda Shiho,
Chihara Kazuo,
Murase Toshio
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(199912)14:6<542::aid-humu15>3.0.co;2-0
Subject(s) - glycogen debranching enzyme , missense mutation , biology , glycogen storage disease , gene , genetics , glycogen , mutation , glycogen synthase , biochemistry
Several different mutations in the glycogen‐debranching enzyme gene AGL have been found in patients with glycogen storage disease type III (GSD III) to date, but no missense mutations have been reported for GSD III, only nonsense, splicing, and deletion/insertion lesions. Here we describe a novel G1448R missense mutation in a Japanese GSD IIIa patient from a consanguineous family. Sequence analysis of cDNA from the patient' liver specimen revealed two separate nucleotide changes: a G‐to‐A transition at nucleotide 3737 in exon 26 (3737G>A) and a G‐to‐C transversion at nucleotide 4742 in exon 33 (4742G>C), both of which result in substitution of glycine by arginine (G1115R and G1448R). Because homo‐zygotes for G1115R were found in healthy controls, G1115R seems to be a polymorphism. Restriction fragment length polymorphism analysis with Bsa JI showed that the patient was homozygous for G1448R and that none of the normal controls had the mutation. This missense mutation is located at a putative glycogen‐binding site that is indispensable for enzyme activity. Thus, G1448R is likely to be the causative mutation in this patient. This is the first report of a missense mutation associated with GSD III. Hum Mutat 14:542–543, 1999. © 1999 Wiley‐Liss, Inc.