GNAS1 유전자 과오돌연변이가 관찰된 가성부갑상선기능저하증 Ia형 1예
A Case of GNAS1 Mutation in Pseudohypoparathyroidism Type Ia
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가성부갑상선기능저하증은 신장의 부갑상선 호르몬에 대한 반응저하를 유발하는 유전질환이다. 가성부갑상선기능저하증 Ia형에서 다양한 GNAS 복합부위의 결손들이 발견되었으며, GNS1 유전자 돌연변이는 Gsα 단백 활성도를 감소시킨다. 대부분의 가성부갑상선기능저하증 Ia형 환자는 특징적으로 알브라이트 유전성 골이영양증(Albright hereditary osteodystrophy)과 저칼슘혈증, 부갑상선호르몬의 증가, Gsα 단백이 매개하는 여러 호르몬들에 대한 저항성을 보인다. 알브라이트 유전성 골이영양증은 작은 신장, 비만, 둥근얼굴형, 피하 석회결절 그리고 발과 손의 단지증 등의 다양한 증상이 발현되는 증후군이다. 저자들은 알브라이트 유전성 골이영양증, 근강축, 어지러움, 빛에 대한 과민성과 시력저하, 인지 및 운동기능의 장애를 보이는 47세 여자환자에서 직접염기서열분석을 통해 국내에서는 최초로 GNAS1 유전자 엑손 6에서 과오돌연변이(c.466G>A,p.Asp156Asn)를 증명하여 가성부갑상선기능저하증 Ia형으로 진단한 증례를 경험하였기에 보고하는 바이다.
Abstract
Pseudohypoparathyroidism (PHP) is a group of genetic disorders in which the kidneys fail to respond to parathyroid hormone. Genetic defects in the GNAS complex locus lead to reduced Gsα (alpha-subunit of the heterotrimeric stimulatory G protein) activity in PHP type Ia patients. These patients exhibit characteristics of Albright hereditary osteodystrophy (AHO) and hypocalcemia, increased parathyroid hormone, and resistance to other Gsα protein-coupled hormones. AHO has a wide range of manifestations such as short stature, obesity, round face, subcutaneous ossification, and bone shortening in the hands and feet. In this study, we present the case of a 47-yr-old woman who was diagnosed with PHP type Ia with AHO. She showed tetany, dizziness, irritability to light, decreased visual acuity, cognitive impairment, and motor dysfunction. Direct sequencing identified a heterozygous missense mutation in exon 6 (c.466G>A, p.Asp156Asn) in GNAS1. To our knowledge, this case is the first report in Korea of PHP type Ia caused by a heterozygous missense mutation in exon 6 (c.466G>A, p.Asp156Asn) in GNAS1.
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