本文選題：假性甲狀旁腺功能減退癥Ia型 + GNAS基因��； 參考：《臨床兒科雜志》2017年08期

【摘要】：目的鑒定導(dǎo)致假性甲狀旁腺功能減退癥(PHP)Ia型發(fā)病的GNAS基因突變。方法回顧分析1例PHP-Ia型患兒的臨床資料。利用Sanger測(cè)序方法對(duì)患兒及其父母GNAS基因的13外顯子進(jìn)行檢測(cè)。疑似致病突變?cè)?78例健康對(duì)照者中進(jìn)行篩查,排除非致病性變異。利用深度測(cè)序方法對(duì)患兒及其父母外周靜脈血的DNA進(jìn)行測(cè)序,分析確定致病突變的起源。結(jié)果女性患兒,實(shí)驗(yàn)室檢查結(jié)果示低血鈣、高血磷及高甲狀旁腺素(PTH);體格檢查有Albright遺傳性骨營(yíng)養(yǎng)不良(AHO)畸形。臨床表現(xiàn)符合PHP-Ia型特征。GNAS基因突變篩查發(fā)現(xiàn)1個(gè)尚未見(jiàn)報(bào)道的,位于6號(hào)外顯子的錯(cuò)義突變(c.479GC,p.R160P)。父母及健康對(duì)照均者未發(fā)現(xiàn)該突變。針對(duì)突變所在的GNAS基因6號(hào)外顯子在患兒及其父母外周靜脈血的DNA中進(jìn)行深度測(cè)序,每個(gè)樣本均獲得8 000條左右的序列�；純焊改傅乃行蛄兄芯Y查到該突變。患兒序列中,3 984條攜帶G等位基因,4 019條攜帶C等位基因,兩者的數(shù)目大致相同。深度測(cè)序的結(jié)果提示,該突變是來(lái)源于母系生殖細(xì)胞的新發(fā)突變。結(jié)論發(fā)現(xiàn)一個(gè)導(dǎo)致PHP-Ia型發(fā)生的GNAS基因新突變(c.479GC,p.R160P),推測(cè)該突變起源于母親生殖細(xì)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.

【作者單位】： 上海市兒科醫(yī)學(xué)研究所上海交通大學(xué)醫(yī)學(xué)院附屬新華醫(yī)院;復(fù)旦大學(xué)生命科學(xué)學(xué)院;上海人類基因組研究中心;濰坊市人民醫(yī)院內(nèi)分泌科;開(kāi)灤總醫(yī)院內(nèi)分泌科;
【基金】：國(guó)家自然科學(xué)基金項(xiàng)目(No.31471190;No.31671317)
【分類號(hào)】：R725.9
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本文編號(hào)：1787159