Correlation of growth hormone receptor and its signal pathway defects with the phenotype: A study of 21 cases with growth hormone insensitivity syndrome
10.3760/cma.j.issn.1000-6699.2015.12.009
- VernacularTitle:21例生长激素不敏感综合征患儿生长激素受体信号通路缺陷与临床关联研究
- Author:
Caiping ZHANG
;
Junqi WANG
;
Ying WANG
;
Wei WANG
;
Zhiya DONG
;
Wei HUANG
;
Defeng WANG
- Publication Type:Journal Article
- Keywords:
Growth hormone insensitivity syndrome;
Growth hormone-insulin-like growth factor-Ⅰ axis;
GHR gene;
IGFALS gene;
JAK2 gene;
STAT5B gene;
Mutation
- From:
Chinese Journal of Endocrinology and Metabolism
2015;31(12):1046-1050
- CountryChina
- Language:Chinese
-
Abstract:
Objective To detect the relationship between the molecular defects and their phenotypes in children with growth hormone insensitivity syndrome (GHIS).Methods 21 patients defined as GHIS were enrolled in the study.4 candidate genes (GHR,IGFALS,JAK2,and STAT5B) were analyzed by genomic DNA sequence screening and clinical relevance analysis.Results The statistical descriptions of the patients were showed as an average height standard deviation (SDS)-4.33 ± 1.91 (-9.17 to-2.21),average serum peak values of GH (22.67 ±20.98) tg/L (11.33 to 104.21 μg/L),basal serum insulin-like growth factor-Ⅰ SDS-2.65 ± 0.53 (-3.57 to -1.79),insulin-like growth factor-binding protein 3 SDS-1.77 ± 1.64 (-4.13 to 0.96).Bone age of backward difference (chronological age-bone age) (43.10 ± 19.54) months (6 to 82 months).One of two children with severe growth failure and mid-face hypoplasia was found to a homozygote for G to A gene mutation in the intron 6 splice donor consensus sequences (IVS6 ds+ 1 G-A) in the GHR gene,causing its functional defect.3 cases with mild dwarf were found gene variations as novel finding:c.1097T＞C c.1098C＞T p.V366A pathogenic variant,c.1229C＞T p.S410L and nt1843707 A→G of 5' UTR region in the IGFALS gene.JAK2 and STAT5b genes mutations were not found.Conclusion Molecular pathology of GHIS is considered as involving the defects of GHR and its signal pathway.The mutation of intron 6 splice donor sequences in GHR gene has been reported which affect the function of GHR.The 3 novel type base variants in IGFALS gene,causing non severe dwarfism,might be suspected with pathogenic roles of GHIS.
