Lab Med Online.  2015 Jan;5(1):38-43. 10.3343/lmo.2015.5.1.38.

A Case of GNAS1 Mutation in Pseudohypoparathyroidism Type Ia

• Park G
• Kim JH
• Rhie SH
• Lee ES
• Noh SE

• KMID: 2312266
• DOI: http://doi.org/10.3343/lmo.2015.5.1.38

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 Gsalpha (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 Gsalpha 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.

Keyword

Albright hereditary osteodystrophy; GNAS1 gene; Missense mutation; Pseudohypoparathyroidism

MeSH Terms

Dizziness
Exons
Female
Foot
Hand
Humans
Hypocalcemia
Kidney
Korea
Mutation, Missense
Obesity
Parathyroid Hormone
Pseudohypoparathyroidism*
Tetany
Visual Acuity
Parathyroid Hormone

Figure

• 

  Fig. 1 The patient had small hands and feet with significantly short digits (A, B). X-ray reveals shortening of metatarsal bones in the feet (C) and metacarpal bones and phalanges in the hands (D).

• 

  Fig. 2 The brain CT scan of the patient of Albright's hereditary osteodystrophy with pseudohypoparathyroidism establishes extensive calcifications in the bilateral dense cerebellum (A) and basal ganglia (B).

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  Fig. 3 Direct sequencing of GNAS1 exon 6 region in the affected patient. A heterozygous G>A substitution at nucleotide position 466 converts an aspartate (GAT) to asparagine (AAT), designated as D156N.

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