糖原累积病Ⅰ b型1例的临床和分子遗传分析

Clinical and molecular genetic analysis for a patient with glycogen storage diseaseⅠ b

目的初步探讨1例糖原累积病Ⅰb型(GSDⅠb)患者的临床特点和致病基因,分析该疾病发生的分子遗传机制。方法收集患者临床资料,抽提患者外周血白细胞基因组DNA,通过多聚酶链反应扩增葡萄糖-6-磷酸酶转位酶基因SLC37A4的9个外显子,用DNA直接测序法确定其突变位点。结果患者临床表现及实验室检查完全符合GSDⅠb。经PCR测序发现SLC37A4基因第3外显子572位碱基C→T纯合突变(c.572 C>T),造成第191位的脯氨酸被亮氨酸替代(p.P191L),导致葡萄糖-6-磷酸转位酶活性下降。结论 SLC37A4基因突变导致的葡萄糖-6-磷酸转位酶结构改变是该GSDⅠb患者临床表现的分子遗传基础。P191L纯合突变在中国大陆的报道尚属首次。相信不久DNA突变分析将会成为糖原累积病Ⅰb型的主要确诊方法。

Objective To analyze the clinical and molecular genetic characteristics of a patient with glycogen storage disease Ⅰb（GSDⅠb）.Methods Genomic DNA was extracted from peripheral leukocytes.All nine exons and the exon-intron boundaries of the SLC37A4 gene were amplified by PCR.The mutations were identified by bidirectional sequencing of the PCR products.Results The patient was diagnosed as GSDⅠb according to the clinical presentations and laboratory examinations,SLC37A4 gene mutation was identified as a homozygous CT transition at nucleotide position 527 of the cDNA.The missense mutation is located in exon 3,codon 191,changing proline to leucine,which changes the conformation of the glucose-6-phosphate translocase（G6PT）.Conclusion Through SLC37A4 gene mutation analysis,the clinical diagnosis of GSDⅠb was confirmed.The alternation of G6PT structure caused by SLC37A4 gene mutation is molecular mechanism to explain clinical manifestation of the patient.To our knowledge,this is the first report of P191L as a cause of GSD1b in Han China mainland and the result suggested that GSDⅠb may be diagnosed based on genomic mutation.