A four-generation pedigree affected with X-linked adrenal hypoplasia congenita due to a novel missense DAX1 mutation.
10.3760/cma.j.issn.1003-9406.2019.05.010
- VernacularTitle:一个X连锁先天性肾上腺发育不良家系的DAX1基因突变研究
- Author:
Zhuona YIN
1
;
Wensheng JIN
2
;
Weiguo XU
3
;
Hongmei LI
2
;
Song ZHANG
4
;
Lingling PENG
5
;
Xiaodong CHEN
6
;
Guangming PENG
7
;
Lixin HAN
8
Author Information
1. Department of Endocrinology, Guangzhou General Hospital of PLA, Guangzhou, Guangdong 510010, China. Department of Endocrinology, the Second People's Hospital of Guangdong Province, Guangzhou, Guangdong, 510317, China.
2. Department of Endocrinology, Guangzhou General Hospital of PLA, Guangzhou, Guangdong 510010, China. Email: vincient301@163.com.
3. Department of Elderly Endocrinology, Guangzhou General Hospital of PLA, Guangzhou, Guangdong 510010, China.
4. Department of Endocrinology, Guangzhou General Hospital of PLA, Guangzhou, Guangdong 510010, China.
5. Department of Pharmacy, Guangzhou General Hospital of PLA, Guangzhou, Guangdong 510010, China.
6. Department of Pathology, Guangzhou General Hospital of PLA, Guangzhou, Guangdong 510010, China.
7. Department of Computer Tomography, Guangzhou General Hospital of PLA, Guangzhou, Guangdong 510010, China.
8. Department of MRI, Guangzhou General Hospital of PLA, Guangzhou, Guangdong 510010, China.
- Publication Type:Journal Article
- MeSH:
Adrenal Insufficiency;
DAX-1 Orphan Nuclear Receptor;
genetics;
Humans;
Hypoadrenocorticism, Familial;
genetics;
Male;
Mutation;
Mutation, Missense;
Pedigree;
Repressor Proteins
- From:
Chinese Journal of Medical Genetics
2019;36(5):456-461
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To report on the clinical pictures of 7 patients from a pedigree affected with X-linked adrenal hypoplasia congenita (XL-AHC) and hypogonadotropic hypogonadism (HH) and the underlying mutations.
METHODS:Seven patients were identified from a four-generation pedigree affected with XL-AHC and HH. Their clinical features, endocrinological changes, treatment and drug response were recorded. The patients were subjected to next-generation sequencing, and the result was verified by Sanger sequencing. PolyPhen-2 was used for predicting the influence of the mutation on protein production.
RESULTS:Three deceased patients had manifested adrenal insufficiency (AI) within one year after birth. Two died at 6 and one died at 12. The four survivors presented with salient clinical and endocrinological features of AHC and HH, adrenal and testicular atrophy, and renin-angiotensin compensation. Two adult patients had testicular micro-stone detected by ultrasound.One of them also had remarkable seminiferous tubule degeneration by biopsy. The patients were followed up for 0.5 to 10 years. All required hyper-physiological dose of hydrocortisone to stabilize their clinical condition. In three patients, gonadotropic or androgen replacement induced cardinal masculine development but with unsatisfactory testis growth and sperm production.Genetic analysis revealed a novel missense c.827A>C (p.Q276P) mutation in a hotspot region within a highly conserved domain. PolyPhen-2 predicted the mutation to be highly hazardous.
CONCLUSION:The novel p.Q276P mutation of the DAX1 gene probably underlies the XL-AHC and HH in this pedigree with variable clinical presentations in the patients.
