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

• Main Authors: Khan Tahir (Author), Klar Joakim (Author), Nawaz Sadia (Author), Jameel Muhammad (Author), Tariq Muhammad (Author), Malik Naveed (Author), Baig Shahid M (Author), Dahl Niklas (Author)
• Format: Book
• Published: BMC, 2012-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1471-2350-13-120; 1471-2350
• Keywords: Anonychia; Hyponychia; Mutation; <it>RSPO4</it> gene; Polymorphism; Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genetics, Vol 13, Iss 1, p 120 (2012)

<p>Abstract</p> <p>Background</p> <p>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 <it>R-spondin 4</it> (<it>RSPO4</it>) gene.</p> <p>Methods</p> <p>Three hypo/anonychia consanguineous Pakistani families were ascertained and genotyped using microsatellite markers spanning the <it>RSPO4</it> locus on chromosome 20p13<b>.</b> Mutation screening of the <it>RSPO4</it> gene was carried out by direct sequencing of the entire coding region and all intron-exon boundaries.</p> <p>Results</p> <p>Mutations in the <it>RSPO4</it> 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.</p> <p>Conclusions</p> <p>This study raises to 17 the number of known <it>RSPO4</it> 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.</p>