Clinical and mutational analysis of 7 children with X-linked adrenal dysplasia congenita.
10.3760/cma.j.issn.1003-9406.2019.06.007
- VernacularTitle:七例X连锁先天性肾上腺发育不良患儿的临床及NROB1基因突变分析
- Author:
Yalei PI
1
;
Yanan ZHANG
;
Yuqian LI
;
Zhanjiang QI
;
Huifeng ZHANG
Author Information
1. Department of Pediatrics, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China. Email: 13333015983@163.com.
- Publication Type:Journal Article
- MeSH:
Adrenal Insufficiency;
Child;
DAX-1 Orphan Nuclear Receptor;
DNA Mutational Analysis;
Genes, X-Linked;
Humans;
Hypoadrenocorticism, Familial;
Male;
Mutation
- From:
Chinese Journal of Medical Genetics
2019;36(6):561-565
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To summarize clinical manifestations, inheritance pattern and mutations of NR0B1 gene in 7 children with X-linked adrenal dysplasia congenita (XL-AHC).
METHODS:Clinical data of the 7 children was collected. Next-generation sequencing was carried out to detect potential mutations in the coding regions of adrenal gland-related genes. Suspected mutations were verified with Sanger sequencing.
RESULTS:In all of the children, the initial symptom was adrenocortical insufficiency. Five cases had neonatal onset, while the remaining two developed it at the age of 2. Three cases (42.9%) had a short stature and 1 showed growth retardation (14.3%). Of the 7 cases, 6 (85.7%) had mutations occurring in exon 1, and 1 (14.3%) had it occurring in exon 2. Four cases (57.1%) were frameshift mutations, 2 cases (28.6%) were nonsense mutations and 1 case (14.3%) was missense mutation. Two mutations were known to be pathogenic, and 5 had not been reported previously. Maternal inheritance was found in 6 cases. Three children had a maternal uncle died of unexplained causes. The mothers of 2 children had a history of spontaneous abortions. One child had a brother died of unexplained reason.
CONCLUSION:Male children with primary adrenal insufficiency should be routinely checked for NR0B1 mutations, especially those with a family history. mutations of NR0B1 gene occur mostly in exon 1, with frameshift mutations being the most common type. The development of all patients with XL-AHC should be closely monitored during follow-up.
