Guanine nucleotide-binding protein α subunit hypofunction in children with short stature and disproportionate shortening of the 4th and 5th metacarpals.
Horm Res Paediatr
; 81(3): 196-203, 2014.
Article
in En
| MEDLINE
| ID: mdl-24481334
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pseudohypoparathyroidism
/
Metacarpal Bones
/
Genetic Loci
/
Growth Disorders
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
Horm Res Paediatr
Journal subject:
ENDOCRINOLOGIA
/
PEDIATRIA
Year:
2014
Document type:
Article
Affiliation country:
Alemania