Identification of ROBO1/2 and SCEL as candidate genes in Kallmann syndrome with emerging bioinformatic analysis

Kallmann syndrome (KS) is a congenital hypogonadotropic hypogonadism that coincides with anosmia or hyposmia. Although this rare genetic disease has a very low incidence, it harbors a complicated genetic heterogeneity, which indicates X-linked, autosomal, and oligogenic inheritance of puberty, sexua...

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Bibliographic Details
Published in:Endocrine 2020, Vol.67 (1), p.224-232
Main Authors: Zhu, Zuobin, Han, Xiaoxiao, Li, Ying, Han, Conghui, Deng, Mengqiong, Zhang, Yuhao, Shen, Qing, Cao, Yijuan, Li, Zhenbei, Wang, Xitao, Gu, Juan, Liu, Xiaoyan, Yang, Yaru, Zhang, Qiang, Hu, Fangfang
Format: Article
Language:English
Subjects:
Anosmia
Cell migration
Chromosome 13
Chromosome 3
Chromosomes
Diabetes
Endocrinology
Etiology
Genomes
Humanities and Social Sciences
Hypogonadism
Internal Medicine
Kallmann's syndrome
Medicine
Medicine & Public Health
multidisciplinary
Original Article
Polygenic inheritance
Puberty
Science
Sexuality
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Summary:Kallmann syndrome (KS) is a congenital hypogonadotropic hypogonadism that coincides with anosmia or hyposmia. Although this rare genetic disease has a very low incidence, it harbors a complicated genetic heterogeneity, which indicates X-linked, autosomal, and oligogenic inheritance of puberty, sexuality, reproductivity, and olfactory defects. There has been limited elucidation of molecular etiologies completed to date. Here, a chromosome reciprocal translocation (46, XX, t (3; 13) (p13; q22)) was identified in a 27-year-old Chinese female diagnosed with KS. Genome sequencing found an intronic breakpoint of SCEL in chromosome 13 and an intergenic breakpoint between ROBO1 and ROBO2 in chromosome 3. This translocation resulted in the reduced expression levels of these genes. An array-CGH test captured no abnormal genomic copy numbers of clinical significance. The basic features of all known KS-related genes were also reviewed and analyzed for their roles in KS onset with bioinformatic methods. Signal pathway and gene enrichment analysis of KS-related genes suggested that these genes have integrated functions in neuronal migration and differentiation. An interesting chromosome locational pattern of KS-related genes was also discovered. This study provided constructive clues for further investigations into the molecular etiology of KS.
ISSN:1355-008X
1559-0100
DOI:10.1007/s12020-019-02010-y