Gollop–Wolfgang Complex Is Associated with a Monoallelic Variation in WNT11-Reference-Cited by-同舟云学术

Gollop–Wolfgang Complex Is Associated with a Monoallelic Variation in WNT11

Published:2024-01-20 Issue:1 Volume:15 Page:129
ISSN:2073-4425
Container-title:Genes
language:en
Short-container-title:Genes

Author:

Odrzywolski Adrian¹²^ORCID,Tüysüz Beyhan³,Debeer Philippe⁴,Souche Erika¹,Voet Arnout⁵,Dimitrov Boyan⁶,Krzesińska Paulina⁷,Vermeesch Joris Robert¹^ORCID,Tylzanowski Przemko⁷⁸

Affiliation:

1. Laboratory for Cytogenetics and Genome Research, Department of Human Genetics, KU Leuven, B-3000 Leuven, Belgium

2. Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland

3. Department of Pediatric Genetics, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey

4. Locomotor and Neurological Disorders, Department of Development and Regeneration, KU Leuven, B-3000 Leuven, Belgium

5. Laboratory of Biomolecular Modelling and Design, Department of Chemistry, KU Leuven, 3001 Heverlee, Belgium

6. Clinical Sciences, Research Group Reproduction and Genetics, Centre for Medical Genetics, Centre for Medical Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium

7. Laboratory of Molecular Genetics, Medical University of Lublin, 20-093 Lublin, Poland

8. Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, B-3000 Leuven, Belgium

Abstract

Gollop–Wolfgang complex (GWC) is a rare congenital limb anomaly characterized by tibial aplasia with femur bifurcation, ipsilateral bifurcation of the thigh bone, and split hand and monodactyly of the feet, resulting in severe and complex limb deformities. The genetic basis of GWC, however, has remained elusive. We studied a three-generation family with four GWC-affected family members. An analysis of whole-genome sequencing results using a custom pipeline identified the WNT11 c.1015G>A missense variant associated with the phenotype. In silico modelling and an in vitro reporter assay further supported the link between the variant and GWC. This finding further contributes to mapping the genetic heterogeneity underlying split hand/foot malformations in general and in GWC specifically.

Funder

NCN

Publisher

MDPI AG

Link

https://www.mdpi.com/2073-4425/15/1/129/pdf

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