Digenic variants of CHD7 and WDR11 in a patient with Kallmann syndrome
10.3760/cma.j.cn311282-20241029-00505
- VernacularTitle:CHD7和WDR11双基因突变导致的卡尔曼综合征
- Author:
Weijia YU
1
;
Yanping DU
1
;
Wenjing TANG
1
;
Minmin CHEN
1
;
Xiaoqing WU
1
;
Xuemei ZHANG
1
;
Liu SHEN
1
;
Qun CHENG
1
Author Information
1. 复旦大学附属华东医院骨质疏松科，上海 200040
- Publication Type:Journal Article
- Keywords:
Kallmann syndrome;
Osteoporosis;
CHD7 gene;
WDR11 gene;
Digenic mutation
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(11):945-952
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.
