GNAS基因新生突变致假性甲状旁腺功能减退症Ia型1例

发布时间：2018-04-22 12:10

  本文选题：假性甲状旁腺功能减退症Ia型 + GNAS基因　； 参考：《临床儿科杂志》2017年08期

【摘要】：目的鉴定导致假性甲状旁腺功能减退症(PHP)Ia型发病的GNAS基因突变。方法回顾分析1例PHP-Ia型患儿的临床资料。利用Sanger测序方法对患儿及其父母GNAS基因的13外显子进行检测。疑似致病突变在478例健康对照者中进行筛查,排除非致病性变异。利用深度测序方法对患儿及其父母外周静脉血的DNA进行测序,分析确定致病突变的起源。结果女性患儿,实验室检查结果示低血钙、高血磷及高甲状旁腺素(PTH);体格检查有Albright遗传性骨营养不良(AHO)畸形。临床表现符合PHP-Ia型特征。GNAS基因突变筛查发现1个尚未见报道的,位于6号外显子的错义突变(c.479GC,p.R160P)。父母及健康对照均者未发现该突变。针对突变所在的GNAS基因6号外显子在患儿及其父母外周静脉血的DNA中进行深度测序,每个样本均获得8 000条左右的序列。患儿父母的所有序列中均筛查到该突变。患儿序列中,3 984条携带G等位基因,4 019条携带C等位基因,两者的数目大致相同。深度测序的结果提示,该突变是来源于母系生殖细胞的新发突变。结论发现一个导致PHP-Ia型发生的GNAS基因新突变(c.479GC,p.R160P),推测该突变起源于母亲生殖细胞。
[Abstract]:Objective to identify the GNAS gene mutations that lead to the onset of pseudohypoparathyroidism (PHP) I a. Methods the clinical data of 1 children with PHP-I a were reviewed and analyzed. The 13 exons of the children and their parents were detected by Sanger sequencing. The suspected pathogenic mutation was screened in 478 healthy controls to exclude non pathogenicity. The DNA of the peripheral venous blood of the children and their parents was sequenced by sequencing, and the origin of the pathogenic mutation was determined. Results in the female children, the results of the laboratory examination showed low blood calcium, high blood phosphorus and hyperthyroidin (PTH), and the physical examination had Albright hereditary malnutrition (AHO) malformation. The clinical manifestations conform to the PHP-Ia type special. 1 unreported mutations (c.479GC, p.R160P) were found in exon 6 (p.R160P). The mutation was not found in both parents and healthy controls. The GNAS gene exon 6 of the mutation was sequenced in the DNA of the peripheral venous blood of the children and their parents, and each sample obtained about 8000 per sample. The sequence. The mutation was screened in all the sequence of the children's parents. In the sequence, 3984 of the G alleles were carried and 4019 carried the C allele, and the number of the two was approximately the same. The result of deep sequencing indicated that the mutation was a new mutation from the maternal germ cell. The conclusion found a new GNAS gene that causes the occurrence of PHP-I a. Mutation (c.479GC, p.R160P) suggests that the mutation originated from mother's germ cells.

【作者单位】： 上海市儿科医学研究所上海交通大学医学院附属新华医院;复旦大学生命科学学院;上海人类基因组研究中心;潍坊市人民医院内分泌科;开滦总医院内分泌科;
【基金】：国家自然科学基金项目(No.31471190;No.31671317)
【分类号】：R725.9
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