A missense mutation in the Na+/glucose cotransporter gene SGLT1 in a patient with congenital glucose-galactose malabsorption:: normal trafficking but inactivation of the mutant protein

被引:40
作者
Kasahara, M [1 ]
Maeda, M
Hayashi, S
Mori, Y
Abe, T
机构
[1] Teikyo Univ, Sch Med, Biophys Lab, Tokyo 1920395, Japan
[2] Teikyo Univ, Genome Res Ctr, Tokyo 1920395, Japan
[3] Fukui Red Cross Hosp, Dept Pediat, Fukui 9188011, Japan
[4] Teikyo Univ, Sch Med, Dept Pediat, Tokyo 1738606, Japan
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2001年 / 1536卷 / 2-3期
关键词
Na+/glucose cotransporter; SGLT1; congenital glucose-galactose malabsorption; protein trafficking;
D O I
10.1016/S0925-4439(01)00043-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Na+/glucose cotransporter gene SGLT1 was analyzed in a Japanese patient with congenital glucose-galactose malabsorption. Genomic DNA was used as a template for amplification by the polymerase chain reaction of each of the 15 exons of SGLT1. The amplification products were cloned and sequenced. About half of the exon 5 clones of the patient contained a C-->T transition, resulting in an Arg(135)-->Trp mutation, whereas the remaining clones contained the normal exon 5 sequence. In addition, whereas some exon 12 clones exhibited the normal sequence, others showed a CAgtaggtatcatc --> CAgacc mutation at the splice donor site of intron 12 that may result either in the skipping of exon 12 or in read-through of intron 12. Neither the Arg(135) --> Trp mutant nor either of the possible intron 12 mutant proteins exhibited Na+-dependent glucose transport activity when expressed in Xenopus oocytes. Immunocytochemical analysis indicated, however, that the Arg(135) --> Trp mutant was localized to the oocyte plasma membrane. DNA sequence analysis revealed that the missense mutation in exon 5 and the splice site mutation in intron 12 were inherited from the proband's father and mother, respectively. These results indicate that the patient is a compound heterozygote for this disease, and that the Arg(135) --> Trp mutant of SGLT1 undergoes normal trafficking to the plasma membrane but is non-functional. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:141 / 147
页数:7
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