A novel IVS2 -2A>T splicing mutation in the GH-1 gene in familial isolated growth hormone deficiency type II in the spectrum of other splicing mutations in the Russian population.
J Clin Endocrinol Metab
; 88(2): 820-6, 2003 Feb.
Article
en En
| MEDLINE
| ID: mdl-12574219
ABSTRACT
Isolated GH deficiency (IGHD) is characterized by genetic heterogeneity, both in familial and sporadic cases. To determine if this statement can be applied to the Russian population, we performed screening for mutations in the GH-1 gene in children living in Russia with IGHD. Twenty-eight children from 26 families with total IGHD were studied. DNA fragments, covering each of four (2-5) exons of GH-1 were amplified using PCR. Single-strand conformation polymorphism analysis followed by direct DNA sequencing identified five heterozygous mutations of splicing in intron 2, intron 3, and exon 4 of GH-1; three of them were not previously reported. We concentrated here on dominant-negative mutations causing IGHD type II, which were as follows 1) A>T transversion of the second base of the 3'-acceptor splice site of intron 2 (IVS2 -2A>T); 2) T>C transition of the second base of the 5'-donor splice site of intron 3 (IVS3 +2T>C); 3) G>A transition of the first base of the 5'-donor splice site of intron 3 (IVS3 +1G>A). Our data indicate allelic heterogeneity of IGHD type II (IGHD II). However, all mutations in Russian IGHD II patients affect splicing, a striking difference from the mutation spectrum of other IGHD forms. The IVS2 -2A>T mutation is the first identified mutation in intron 2 of GH-1. The 5'-donor splice site of intron 3 of GH-1 is a mutational hot spot, and the IVS3 +1G>A mutation can be considered to be a common molecular defect in IGHD II in Russian patients.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Empalme del ARN
/
Mutación Puntual
/
Hormona de Crecimiento Humana
Límite:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
País/Región como asunto:
Asia
/
Europa
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2003
Tipo del documento:
Article
País de afiliación:
Rusia