Clinical and Genetic Analysis in Chinese Families with Synpolydactyly, and Cellular Localization of HOXD13 with Different Length of Polyalanine Tract

Overview

Journal Front Genet

Date 2023 Apr 10

PMID 37035736

Authors

Xiumin Chen

Feiyue Zhao

Yiming Xu

Yixuan Cao

Shan Li

Xue Zhang

Xiuli Zhao

Affiliations

Soon will be listed here.

Abstract

Synpolydactyly (SPD) is caused by mutations in the transcription factor gene . Such mutations include polyalanine expansion (PAE), but further study is required for the phenotypic spectrum characteristics of PAE. We investigated four unrelated Chinese families with significant limb malformations. Three PAEs were found in the polyalanine coding region: c.172_192dup (p.Ala58_Ala64dup) in Family 1, c.169_192dup (p.Ala57_Ala64dup) in Family 2, and c.183_210dup (p.Ala62_Ala70dup) in Family 3 and Family 4. Interestingly, we identified a new manifestation of preaxial polydactyly in both hands in a pediatric patient with an expansion of seven alanines, a phenotype not previously noted in SPD patients. Comparing with the wild-type cells and mutant cells with polyalanine contractions (PACs), the HOXD13 protein with a PAE of nine-alanine or more was difficult to enter the nucleus, and easy to form inclusion bodies in the cytoplasm, and with the increase of PAE, the more inclusion bodies were formed. This study not only expanded the phenotypic spectrum of SPD, but also enriched our understanding of its pathogenic mechanisms.

Citing Articles

New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis.

Chen X, Shen X, Yang T, Cao Y, Zhao X BMC Med Genomics. 2024; 17(1):259.

PMID: 39472920 PMC: 11523653. DOI: 10.1186/s12920-024-01974-9.

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