| Summary: | 碩士 === 國立臺灣大學 === 分子醫學研究所 === 96 === Pseudohypoparathyroidism is an autosomal dominant disease characterized by hypocalcemia and hyperphosphatemia duo to target-organ resistance to parathyroid hormone (PTH). PHP-Ia ( Pseudohypoparathyroidism-Ia ) is the most frequent type of PHP . Patients with PHP-Ia often present with additional hormonal resistance and show characteristic physical features that are collectively termed AHO ( Albright’s hereditary osteodystrophy , a congenital syndrome in which patients develop short stature、round face、obesity、 brachydactyly、heterotopic ossification , and mental retardation ). PHP-Ia is caused by heterozygous inactivating mutations located in GNAS1 gene that mapped to chromosome 20q13.11, which encoding the α subunit of the stimulatory guanine nucleotide-binding protein (Gsα) . They show a partial deficiency of Gs activity and function. To data , over 50 different mutations in GNAS1 have been identified distributed in Germany、Italy、USA、England、Hong Kong and Japan . Regarding molecular analysis , almost seventy percent patients carry detectable GNAS1 mutations , but still thirty unknown so far.
This thesis included three individuals from unrelated families and one PHP-Ia family , Here described the first mutational analysis of GNAS1 in Taiwan PHP-Ia patients , we found a novel heterozygous missense mutation I106T in exon5 , revealed associated with substitution of threonine for isoleucine at codon 106 , the mutation had not been reported previously .
Furthermore , we hope set up a model of genetic testing and counseling for PHP-Ia based on this study , contribute highly medical supplyment and consultation in the future .
|
|---|
