Analysis ofGNAS gene variant in a Chinese pedigree affected with pseudohypoparathyroidism
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目的 探讨1个假性甲状旁腺功能减退症家系的遗传学病因。 方法 选取2020年12月26日于河南省人民医院就诊的1个假性甲状旁腺功能减退症家系为研究对象。采用家系全外显子组测序(trio-WES)对先证者及其父母进行分析，筛选候选变异。随机选取50名健康个体进行限制性片段长度多态性检测，以排除基因位点多态性。采用短串联重复序列(STR)连锁分析确定致病变异的亲代来源。 结果 Trio-WES及Sanger测序结果显示先证者及母亲均携带GNAS基因c.121C>G(p.His41Asp)变异，家系其余成员及健康对照人群均未发现相同变异，检索数据库未见收录。依据美国医学遗传学与基因组学学会相关指南判断为可能致病变异。 结论 GNAS基因c.121C>G(p.His41Asp)变异可能是该家系的遗传学病因。上述发现丰富了GNAS基因的变异谱。 Objective To explore the genetic etiology of a Chinese pedigree affected with pseudohypoparathyroidism. Methods Peripheral blood samples of the proband and his parents were collected and subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified among the pedigree and 50 randomly selected healthy individuals through analysis of restriction fragment length polymorphism. Short tandem repeat (STR) linkage analysis was used to verify the parental origin of the pathogenic variants. Results Trio-WES and Sanger sequencing showed that the proband and his mother had both harbored a c. 121C>G (p.His41Asp) variant of theGNAS gene, which was not found in other family members and the 50 healthy controls. The variant was not found in international databases. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic. Conclusion The novel c. 121C>G variant of theGNAS gene probably underlay the disease in this pedigree. Above finding has enriched the spectrum of GNAS gene variants.
Objective To explore the genetic etiology of a Chinese pedigree affected with pseudohypoparathyroidism. Methods Peripheral blood samples of the proband and his parents were collected and subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified among the pedigree and 50 randomly selected healthy individuals through analysis of restriction fragment length polymorphism. Short tandem repeat (STR) linkage analysis was used to verify the parental origin of the pathogenic variants. Results Trio-WES and Sanger sequencing showed that the proband and his mother had both harbored a c. 121C>G (p.His41Asp) variant of theGNAS gene, which was not found in other family members and the 50 healthy controls. The variant was not found in international databases. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic. Conclusion The novel c. 121C>G variant of theGNAS gene probably underlay the disease in this pedigree. Above finding has enriched the spectrum of GNAS gene variants.
PseudohypoparathyroidismGNAS geneWhole exome sequencingShort tandem repeat
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