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Novel missense mutation in the RSPO4 gene in congenital hyponychia and evidence for a polymorphic initiation codon (p.M1I)

Tahir Naeem Khan1, Joakim Klar2, Sadia Nawaz1, Muhammad Jameel1, Muhammad Tariq1, Naveed Altaf Malik1, Shahid M Baig1 and Niklas Dahl2*

Author Affiliations

1 Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, 38000, Pakistan

2 Department of Immunology, Genetics and Pathology, The Rudbeck Laboratory and Science for Life Laboratory, Uppsala University, Uppsala, 751 85, Sweden

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BMC Medical Genetics 2012, 13:120  doi:10.1186/1471-2350-13-120

Published: 13 December 2012



Anonychia/hyponychia congenita is a rare autosomal recessive developmental disorder characterized by the absence (anonychia) or hypoplasia (hyponuchia) of finger- and/or toenails frequently caused by mutations in the R-spondin 4 (RSPO4) gene.


Three hypo/anonychia consanguineous Pakistani families were ascertained and genotyped using microsatellite markers spanning the RSPO4 locus on chromosome 20p13. Mutation screening of the RSPO4 gene was carried out by direct sequencing of the entire coding region and all intron-exon boundaries.


Mutations in the RSPO4 gene were identified in all families including a novel missense mutation c.178C>T (p.R60W) and two recurrent variants c.353G>A (p.C118Y) and c.3G>A (p.M1I). The c.3G>A variant was identified in unaffected family members and a control sample in a homozygous state.


This study raises to 17 the number of known RSPO4 mutations and further expands the molecular repertoire causing hypo/anonychia. The c.353G>A emerges as a recurrent change with a possible founder effect in the Pakistani population. Our findings suggest that c.3G>A is not sufficient to cause the disorder and could be considered a polymorphism.

Anonychia; Hyponychia; Mutation; RSPO4 gene; Polymorphism