Novel NECTIN4 Mutations in Ectodermal Dysplasia Syndactyly Syndrome in Two Families
Dania Abu Assab1, Abraham Zlotogorski1, Vered Molho-Pessach1
1Department of Dermatology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
The Israel Medical Association Journal : IMAJ
|June 30, 2025
Summary
Two new NECTIN4 gene mutations were identified in families with ectodermal dysplasia-syndactyly syndrome (EDSS). This study expands the understanding of genetic causes for this rare disorder.
Area of Science:
- Genetics
- Molecular Biology
- Dermatology
Background:
- Ectodermal dysplasia-syndactyly syndrome (EDSS) is a rare genetic disorder.
- EDSS is caused by mutations in the NECTIN4 (also known as PVRL4) gene.
Purpose of the Study:
- To identify novel and rare mutations in the NECTIN4 gene.
- To investigate two unrelated families diagnosed with EDSS.
Main Methods:
- Genetic analysis of six patients from two families using next-generation and Sanger sequencing.
- Literature review to identify previously reported EDSS cases.
Main Results:
- A homozygous mutation (c.680A>G p.His227Arg) and a novel compound heterozygous mutation (c.79+1G>A) in NECTIN4 were identified in affected individuals.
- Both identified mutations impact the extracellular domain of the nectin-4 protein.
- Only 13 families with EDSS have been previously reported in the literature.
Conclusions:
- Two families with six affected members presented with EDSS due to two novel NECTIN4 mutations.
- The study contributes to the understanding of the genetic basis of EDSS.
- A review of existing medical literature on EDSS was conducted.
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