Deciphering the Mutational Signature of Congenital Limb Malformations

Overview

Journal Mol Ther Nucleic Acids

Publisher Cell Press

Date 2021 Jun 7

PMID 34094714

Citations 5

Authors

Liying Sun

Yingzhao Huang

Sen Zhao

Junhui Zhao

Zihui Yan

Yang Guo

Mao Lin

Wenyao Zhong

Yuehan Yin

Zefu Chen

Nan Zhang

Yuanqiang Zhang

Zongxuan Zhao

Qingyang Li

Lianlei Wang

Xiying Dong

Yaqi Li

Xiaoxin Li

Guixing Qiu

Terry Jianguo Zhang

Zhihong Wu

Wen Tian

Nan Wu

Affiliations

Soon will be listed here.

Abstract

Congenital limb malformations (CLMs) affect 1 in 500 live births. However, the value of exome sequencing (ES) for CLM is lacking. The purpose of this study was to decipher the mutational signature of CLM on an exome level. We enrolled a cohort of 66 unrelated probands (including 47 families) with CLM requiring surgical correction. ES was performed for all patients and available parental samples. A definite molecular diagnosis was achieved in 21 out of 66 (32%) patients. We identified 19 pathogenic or likely pathogenic single-nucleotide variants and three copy number variants, of which 11 variants were novel. We identified four variants of uncertain significance. Additionally, we identified and as novel candidate genes for CLM. By comparing the detailed phenotypic features, we expand the phenotypic spectrum of diastrophic dysplasia and chromosome 6q terminal deletion syndrome. We also found that the diagnostic rate was significantly higher in patients with a family history of CLM (p = 0.012) or more than one limb affected (p = 0.034). Our study expands our understanding of the mutational and phenotypic spectrum of CLM and provides novel insights into the genetic basis of these syndromes.

Citing Articles

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