Abstract
Ectodermal-dysplasia-syndactyly syndrome (EDSS1) is a rare form of ectodermal dysplasia (ED), affecting skin and its appendages mainly hair, teeth and nails. In the present study, we have investigated a large consanguineous Pakistani family with 10 individuals showing features of EDSS1. Human genome was screened using highly polymorphic microsatellite markers to identify the gene causing EDSS1. The disease locus for EDSS1 was assigned to chromosome 1q23.1-q23.3. This region corresponds to 5.63 Mb according to the sequenced based physical map (Build 36.2) of the human genome and flanked by markers D1S1653 and D1S1677. A maximum two-point LOD score of 5.05 was obtained with the marker D1S484. Sequence analysis revealed a homozygous missense mutation (c.635C>G; p.Pro212Arg) in the recently reported PVRL4 gene causing EDSS1. The involvement of mutant nectin-4 in causing EDSS1 may open up interesting prospectives into the role of cell adhesion molecules in causing syndromic forms of EDs.
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Acknowledgements
We are grateful to all the members of the family for their invaluable participation and cooperation. Funding: the work presented here was funded by Higher Education Commission (HEC), Islamabad, Pakistan. Musharraf Jelani was supported by an indigenous PhD fellowship from HEC, Islamabad, Pakistan.
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Jelani, M., Chishti, M. & Ahmad, W. Mutation in PVRL4 gene encoding nectin-4 underlies ectodermal-dysplasia-syndactyly syndrome (EDSS1). J Hum Genet 56, 352–357 (2011). https://doi.org/10.1038/jhg.2011.18
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DOI: https://doi.org/10.1038/jhg.2011.18
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