Reis Mariana Tenorio Antunes, Cattani Andreina, Mendonca Berenice Bilharinho, Corrêa Pedro Henrique Silveira, Martin Regina Matsunaga
Diseases Unit Osteometabolic, Endocrinology Service, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil.
Arq Bras Endocrinol Metabol. 2010 Nov;54(8):728-31. doi: 10.1590/s0004-27302010000800011.
The objective of this study was to describe a new mutation in GNAS in a family with pseudohypoparathyroidism type Ia (PHP Ia), a rare osteometabolic disease. An 8-month-old boy was seen by an Endocrinologist due to obesity and low growth velocity. Noteworthy, his mother exhibited typical Albright hereditary osteodystrophy (AHO) phenotype. The clinical diagnosis of PHP Ia was suspected. The GNAS coding region from mother and son was amplified and directly sequenced. A novel heterozygous missense mutation (c.673T>C) was identified in exon 5 in both patients. In this family, the mother's clinical picture was the clue for the son's diagnosis. Molecular analysis of GNAS confirmed the diagnosis of PHP Ia in both patients and the child's early diagnosis was possible. Moreover, this novel missense substitution expands the spectrum of GNAS mutations associated with this disorder and allows for genetic counseling of this family.
本研究的目的是描述1型假性甲状旁腺功能减退症（PHP Ia）患者家族中GNAS基因的一种新突变，PHP Ia是一种罕见的骨代谢疾病。一名8个月大的男孩因肥胖和生长速度缓慢被内分泌科医生诊治。值得注意的是，他的母亲表现出典型的奥尔布赖特遗传性骨营养不良（AHO）表型。怀疑为PHP Ia的临床诊断。对母亲和儿子的GNAS编码区进行扩增并直接测序。在两名患者的第5外显子中均鉴定出一种新的杂合错义突变（c.673T>C）。在这个家族中，母亲的临床表现是儿子诊断的线索。GNAS的分子分析证实了两名患者均为PHP Ia，并且该患儿得以早期诊断。此外，这种新的错义替代扩展了与该疾病相关的GNAS突变谱，并可为这个家族提供遗传咨询。
