A c.3216_3217delGA mutation in AGL gene in Tunisian patients with a glycogen storage disease type III: evidence of a founder effect

被引：5

作者：

Mili, A. ^{[1
,3
]}

Ben Charfeddine, I. ^{[1
]}

Amara, A. ^{[1
]}

Mamai, O. ^{[1
]}

Adala, L. ^{[1
]}

Ben Lazreg, T. ^{[1
]}

Bouguila, J. ^{[2
]}

Saad, A. ^{[1
]}

Limem, K. ^{[3
]}

Gribaa, M. ^{[1
]}

机构：

[1] Farhat Hached Univ Hosp, Lab Human Cytogenet Mol Genet & Reprod Biol, Sousse 4000, Tunisia

[2] Farhat Hached Univ Hosp, Dept Paediat, Sousse 4000, Tunisia

[3] Univ Sousse, Fac Med, Dept Biochem, Sousse, Tunisia

来源：

CLINICAL GENETICS | 2012年 / 82卷 / 06期

关键词：

AGL gene; amylo-1,6-glucosidase; founder effect; glycogen storage disease type III; haplotype study; mutation; Tunisian patients; DEBRANCHING ENZYME GENE; EXON; 3; DIAGNOSIS; IDENTIFICATION; DEFICIENCY; FEATURES; REGION; LIVER;

D O I：

10.1111/j.1399-0004.2011.01806.x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Glycogen storage disease type III (GSD III) is an autosomal recessive disorder characterized by excessive accumulation of abnormal glycogen in the liver and muscles and caused by deficiency in the glycogen debranching enzyme, the amylo-1,6-glucosidase (AGL). In this study, we report the clinical, biochemical and genotyping features of five unrelated GSD III patients coming from the same region in Tunisia. The concentration of erythrocyte glycogen and AGL activity were measured by colorimetric and fluorimetric methods, respectively. Four CA/TG microsatellite markers flanking the AGL gene in chromosome 1 were amplified with fluoresceinated primers. The full coding exons and their relevant exonintron boundaries of the AGL gene were directly sequenced for the patients and their parents. All patients showed a striking increase of erythrocytes glycogen content. No AGL activity was detected in peripheral leukocytes. Sequencing of the AGL gene identified a c.3216_3217delGA (p.Glu1072AspfsX36) mutation in the five patients which leads to a premature termination, abolishing the AGL activity. Haplotype analysis showed that the mutation was associated with a common homozygote haplotype. Our results suggested the existence of a founder effect responsible for GSD III in this region of Tunisia.

引用

页码：534 / 539

页数：6