假性甲状旁腺功能减退症Ia型遗传学研究——附一家系报告

Genetic analysis of pseudohypoparathyroidism type I a ： report of a pedigree

回顾性分析1例假性甲状旁腺功能减退症（PHP）Ia型患者及其家系成员的临床及遗传学资料。先证者具有Albright遗传性骨营养不良症（AHO）的特征性表现，低钙，高磷，对多重激素如PTH和TSH抵抗，其哥哥和父母无异常临床表现。予补钙及维生素D治疗后，患者癫痫症状明显好转，但AHO畸形无明显变化。对患者及其哥哥、父母的GNASl基因进行测序，将所有基因序列与文献报道和GenBank数据库序列进行比对，发现患者及其母亲的GNASl基因第13号外显子c.1107_1108delTG（p．Glu370Argfs X11）位点存在（杂合）框移突变。提示该框移突变可能导致患者PHPIa型发病。

The clinical and genetic data were retrospectively analyzed in a pedigree with pseudohypoparathyroidism type ] a. Clinically typical Albright hereditary osteodystrophy （AHO） , hypocalcemia, hyperphosphatemia, and PTH- and TSH-resistance were manifested in the proband, but not in his brother and parents. The proband＇s symptom of epilepsy was alleviated by treatment with calcium and vitamin D, which was of no avail in regard to AHO. After GNAS1 genes were sequenced and compared with the GenBank data among the family members, a deletion of c. 1107_1108 （ p. Glu370ArgfsX11 ） in exon 13 of GNAS1 gene leading to a frameshift mutation was found in the proband and his mother. It suggested that the GNAS1 gene mutation might be related to the pathogenesis of the disease.