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Horm Res Paediatr. 2014;81(3):196-203. doi: 10.1159/000356928. Epub 2014 Jan 25.

Guanine nucleotide-binding protein α subunit hypofunction in children with short stature and disproportionate shortening of the 4th and 5th metacarpals.

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1
Division of Paediatric Endocrinology, University Children's Hospital Heidelberg, Heidelberg, Germany.

Abstract

BACKGROUND:

GNAS encodes the α subunit of the stimulatory G protein (Gsα). Maternal inherited Gsα mutations cause pseudohypoparathyroidism type Ia (PHP-Ia), associated with shortening of the 4th and 5th metacarpals.

AIMS:

Here we investigated the Gsα pathway in short patients with distinct shortening of the 4th and 5th metacarpals.

METHODS:

In 571 children with short stature and 4 patients with PHP-Ia metacarpal bone lengths were measured. In identified patients we analysed the Gsα protein function in platelets, performed GNAS sequencing, and epigenetic analysis of four significant differentially methylated regions.

RESULTS:

In 51 patients (8.9%) shortening of the 4th and 5th metacarpals was more pronounced than their height deficit. No GNAS coding mutations were identified in 20 analysed patients, except in 2 PHP-Ia patients. Gsα activity was reduced in all PHP-Ia patients and in 25% of the analysed patients. No significant methylation changes were identified.

CONCLUSIONS:

Our findings suggest that patients with short stature and distinct metacarpal bone shortening could be part of the wide variety of PHP/PPHP, therefore it was worthwhile analysing the Gsα protein function and GNAS gene in these patients in order to further elucidate the phenotype and genotype of Gsα dysfunction.

PMID:
24481334
DOI:
10.1159/000356928
[Indexed for MEDLINE]
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