家族性副甲狀腺功能低下之GCMB基因分析

Abstract

副甲狀腺功能低下症(hypoparathyroidism， HP)的特徵是低血鈣和高血磷，由於PTH的分泌不足或缺乏所造成的。單一家族性副甲狀腺功能低下(Familial isolated hypoparathyroidism )可能由幾種基因突變有關，如：GCMB 基因(MIN 603716）、CaSR 基因 (MIN 601199)、GATA3基因（MIN131320）、PTH 基因(MIN 168450)。遺傳模式為自體顯性(autosomoal dominant)、自體隱性(autosomoal recessive)或X染色體連鎖(X chromosome-linked)遺傳。從文獻得知GCMB是一種轉錄因子，且在副甲狀腺的發育扮演重要的角色。故本研究是以一個HP家族中兩位已知檢測過CaSR和GATA3基因的HP病患，取週邊血液萃取total DNA，進行所有GCMB的外顯子（exon）的序列分析。結果發現其中一位病患在exon 5 第323鹽基位置的C轉變成T，此點突變轉錄後並未改變胺基酸，所以此病患的GCMB的exon 5上的突變與HP是沒有關係的。由於這兩位病患已檢測過GCMB 、CaSR及GATA3基因，未來希望能分析與副甲狀腺發育相關的基因突變，藉此建立基因檢測與遺傳諮詢模式。

Hypoparathyroidium (HP) is characterized by hypocalcemia and hyperphosphatemia due to deficient or absent secretion of parathyroid hormone (PTH). Familial isolated hypoparathyroidism (FIH) is associated with the mutation of several gene, including GCMB (MIN 603716), CaSR (MIN 601199), GATA3 (MIN 131320), and PTH (MIN 168450). FIH could be autosomoal dominant, autosomal recessive or X choromosome-linked in mode of inheritance. GCMB is identified as a transcription factor and plays a role in parathyroid gland development. Our study was to examine the GCMB gene in two HP patients of a HP family, who CaSR and GATA3 have been found to have no mutations. We identified a C to T at nucleotide position 323 in exon 5, present in one HP patient, and this point mutation was a nonsense mutation, so exon 5 of GCMB mutation in HP patient was not associated with HP. In future, we win analyze sequence of the other gene that are involved in the development of the parathyroid glands, and then establish a model of mutation detection and genetic counseling.