Identification of ROBO1/2 and SCEL as candidate genes in Kallmann syndrome with emerging bioinformatic analysis
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ORIGINAL ARTICLE
Identification of ROBO1/2 and SCEL as candidate genes in Kallmann syndrome with emerging bioinformatic analysis Zuobin Zhu 1 Xiaoxiao Han2 Ying Li3 Conghui Han4 Mengqiong Deng5 Yuhao Zhang6 Qing Shen5 Yijuan Cao5,7 Zhenbei Li5,7 Xitao Wang4 Juan Gu5,7 Xiaoyan Liu5,7 Yaru Yang5,7 Qiang Zhang1 Fangfang Hu5,7 ●
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Received: 22 April 2019 / Accepted: 9 July 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract 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.
Introduction Congenital hypogonadotropic hypogonadism (CHH) occurs in about 1/10,000 of men and 1/50,000 of women with an increasing incidence currently being witnessed [1, 2]. When associated with anosmia/hyposmia, CHH is referred to as Kallmann syndrome (KS). KS exhibits significant genetic heterogeneity with more than 20 susceptible genes [3]. The
These authors contributed equally: Zuobin Zhu, Xiaoxiao Han
inheritance patterns of KS vary drastically, representing autosomal, X-linked, and oligogenic modes, that lead to defects in puberty, sexuality, reproductivity, and olfactory development. There have been limited molecular etiologies revealed in previous research [3]. In many cases, the disorder is obscure for doctors to identify when performing casual pedigree analysis, because there are challenges sorting out logical gene transmission pathways and matching gene mutations to phenotypes, especially when atypical symptoms are considered [4]. Such difficulties not only originate from the number of responsible genes associated with KS, whose number of identified genes is still
* Qiang Zhang [email protected]
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* Fangfang Hu [email protected]
Medical Technology Coll
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