Genotype-phenotype and genetic analysis in five patients with Kallmann syndrome
10.3760/cma.j.cn311282-20210427-00261
- VernacularTitle:五例Kallmann综合征患者的基因型-表型关系和遗传学研究
- Author:
Junke XIA
1
;
Xiao LUO
;
Jing WU
;
Peng DAI
;
Yanxia LIU
;
Yanjie XIA
;
Peiyi XIA
;
Xiangdong KONG
Author Information
1. 郑州大学第一附属医院妇产科遗传与产前诊断中心 450052
- Keywords:
Kallmann syndrome;
Hypogonadotropic hypogonadism;
Anosmia;
Whole exome sequencing
- From:
Chinese Journal of Endocrinology and Metabolism
2021;37(12):1106-1111
- CountryChina
- Language:Chinese
-
Abstract:
To study the genotype-phenotype and genetic characteristics of Kallmann syndrome. Five patients with Kallmann syndrome were enrolled. Clinical data collection, chromosome karyotyping, whole exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA) were used. All the five patients were males, aging from 2 months to 45 years old. Three of the five patients complained cryptorchidism, one complained gonadal dysgenesis, and one complained fasting hyperglycemia. The clinical feature was hypogonadotropic hypogonadism with anosmia, and all karyotype was 46 XY. Magnetic resonance imaging (MRI) showed undeveloped olfactory bulbs and tracts. Kallmann syndrome related gene novel variants were found in all the 5 patients. The hypoplasia of right kidney was found in a patient with c. 1795_1799del (p.Asn599Profs*66) of anosmin 1 (ANOS1) variant. Clinical heterogeneity and incomplete penetrance were seen in a patient with c. 2824A>G (p.Thr942Ala) of chromodomain helicase DNA binding protein 7 (CHD7). Besides, WES indicated a 109 bp-deletion on Xp22.31 (chrX: 8507699-8507804), which was the deletion of exon 10 on ANOS1 gene verified by MLPA. The deletion variant was inherited form his mother, and conformed to X-linked recessive inheritance. Kallmann syndrome is genetic and clinical heterogeneous. WES is helpful for early diagnosis. MLPA and genome copy number variation analysis (CNV) are also recommend if necessary.
