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ORIGINAL RESEARCH article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1399604

Deciphering the Genomic Insights into the Coexistence of Congenital Scoliosis and Congenital Anomalies of the Kidney and Urinary Tract

Provisionally accepted
Haojun Wang Haojun Wang 1Wen Wen Wen Wen 2Mingxi Yao Mingxi Yao 1Tongwang Yang Tongwang Yang 3Dongshan Chen Dongshan Chen 1*Wei Wang Wei Wang 1*
  • 1 Beijing Chaoyang Hospital, Capital Medical University, Beijing, Beijing Municipality, China
  • 2 Chinese Academy of Sciences (CAS), Beijing, Beijing, China
  • 3 Changsha Medical University, Changsha, Hunan Province, China

The final, formatted version of the article will be published soon.

    Congenital scoliosis and congenital anomalies of the kidney and urinary tract are distinct genetic disorders with differing clinical manifestations. Clinically, their coexistence is not rare, but the etiologies of these complex diseases remain largely unknown, especially their shared genetic basis.We sequenced the genomes of 40 individuals diagnosed with both CS and CAKUT, alongside 2,764 controls from a Chinese Han population cohort. Our analyses encompassed gene-based and pathwaybased weighted rare variant association tests, complemented by copy number variant association analyses, aiming to unravel the shared genomic etiology underlying these congenital conditions.Gene-based analysis identified PTPN11 as a pivotal gene influencing both skeletal and urinary system development (P = 1.95E-21), participating in metabolic pathways, especially the MAPK/ERK pathway known to regulate skeletal and urinary system development. Pathway-based enrichment showed a significant signal in the MAPK/ERK pathway (P = 3E-04), reinforcing the potential role of PTPN11 and MAPK/ERK pathway in both conditions. Additionally, CNV analysis pinpointed IGFLR1 haploinsufficiency as a potential influential factor in the combined CS-CAKUT phenotypic spectrum.This study enriches our understanding of the intricate genomic interplay underlying congenital scoliosis and kidney and urinary tract anomalies, emphasizing the shared genetic foundations between these two disorders.

    Keywords: Congenital scoliosis (CS), CAKUT, mutational burden analysis, Molecular etiology, Ptpn11, CNV association Congenital scoliosis (CS), CNV association

    Received: 12 Mar 2024; Accepted: 02 Jul 2024.

    Copyright: © 2024 Wang, Wen, Yao, Yang, Chen and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Dongshan Chen, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100001, Beijing Municipality, China
    Wei Wang, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100001, Beijing Municipality, China

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