婴儿持续性高胰岛素血症性低血糖症9例临床和基因突变分析

目的分析婴儿持续性高胰岛素血症性低血糖症(PHHI)的临床表现、遗传学特点和基因突变特点。从基因水平了解PHHI的致病因素,以达到基因诊断和遗传咨询的目的。方法对9例PHHI患儿临床表现及检查结果进行分析。提取患儿外周血基因组DNA,利用聚合酶链式反应(PCR)先扩增外周血ABCC8和KCNJ11基因外显子所在片段,对扩增片段进行正向序列测定,以检测突变。结果 2例患儿KCNJ11基因突变,1例患儿KCNJ11外显子第101位点G→A纯合突变(R34H),1例患儿KCNJ11外显子第91位点C→T杂合突变(R31W);2例患儿ABCC8基因突变,1例患儿ABCC8外显子31第3832位点出现G→A杂合突变(G1255S),1例患儿AB-CC8外显子12第1861位点出现C→T杂合突变(R598X)。结论发现4例患儿的基因突变,并发现一个国内外尚未见报道的ABCC8新突变(G1255S),为临床治疗、遗传咨询及产前诊断提供依据。

Clinic and gene mutation analysis on 9 cases of persistent hyperinsulinemic hypoglycemia of infancy

Objective To analyze the clinic and genetic characteristics of persistent hyperinsulinemic hypoglycemia of infancy(PHHI) caused by ABCC8 and KCNJ11 gene mutation,thus to provide a practical method for genetic diagnosis and counseling.Methods Clinical manifestations and laboratory test results of the 9 patients with PHHI were collected.Genomic DNA from peripheral blood was collected for genetic analysis in these patients.ABCC8 and KCNJ11 exon gene from peripheral blood was amplified by polymerase chain reaction(PCR) and sequenced for detection of mutation.Results ABCC8 gene and KCNJ11 gene mutations were found in 2 cases each.A missense mutation of R34H(101G→A) in exon of KCNJ11 gene,which was a homozygotic mutation,was identified in Patient 4.A missense mutation of R31W(91C→T) in exon of KCNJ11 gene,which was a heterozygotic mutation,was identified in Patient 5.A noval mutation of G1255S(3832G→A) in exon 31 of ABCC8 gene,which was a heterozygotic mutation,was identified in Patient 3.A nonsense mutation of R598X(1861C→T) in exon 12 of ABCC8 gene,which was a heterozygotic mutation,was identified in Patient 9.Conclusion Four patients were identified with gene mutation.G1255S of ABCC8 gene is a new mutation firstly reported.Gene mutation analysis is important for prenatal diagnosis,genetic counseling and clinic management.