A rare Gollop-Wolfgang Syndrome linked to a mutation in Wnt11-Reference-Cited by-同舟云学术

A rare Gollop-Wolfgang Syndrome linked to a mutation in Wnt11

Published:2023-05-25 Issue: Volume: Page:
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Author:

Odrzywolski Adrian¹,Tüysüz Beyhan²,Debeer Philippe³,Souche Erika⁴,Voet Arnout⁵,Dimitrov Boyan Ivanov⁶,Krzesińska Paulina⁷,Vermeesch Joris Robert⁴,Tylzanowski Przemko⁸

Affiliation:

1. Department of Biochemistry and Molecular Biology, Medical University of Lublin

2. Department of Pediatric Genetics, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine

3. Locomotor and Neurological Disorders, Department of Development and Regeneration

4. Laboratory for Cytogenetics and Genome Research, Department of Human Genetics

5. Laboratory of Biomolecular Modelling and Design, Department of Chemistry

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

7. Laboratory of Molecular Genetics, Medical University of Lublin

8. Skeletal Biology and Engineering Research Center, Department of Development and Regeneration

Abstract

Abstract Gollop-Wolfgang syndrome (GWS) is a rare congenital limb anomaly of unknown genetic background, characterized by a tibial aplasia, ipsilateral bifurcation of the thigh bone, and an ectrodactyly. A phenotypically similar condition is called Split-hand/foot malformation associated with aplasia of long bones (SHFLD). Several hotspots on chromosome 17 have been linked to SHFLD phenotype. Some of them, like duplications described within BHLHA9, are associated both with ectrodactyly and tibial aplasia. Nonetheless, no single mutation linking all known GWS patients has been identified yet. We studied a three-generation family with four GWS-affected family members. Analysis of whole genome sequencing with a custom pipeline indicated that WNT11 c.1015G>A mutation could cause the observed phenotype. Further, in silico modeling and luciferase assay supported WNT11 c.1015G>A mutation effect on Wnt11 functionality.

Publisher

Research Square Platform LLC

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