Autosomal recessive pachyonychia congenita

The molecular genetic analysis of the expanding pachyonychia congenita case collection

“…In five of these (families [16][17][18][19][20] mutations were at the intron 1/exon 2 boundary of K6a; three different sequence changes were identified, all of which we have reported previously, 16 but at that time, owing to the unavailability of mRNA, we were unable to identify the mutations at the protein level. However, in this study we obtained mRNA from a skin biopsy from an affected individual from family 17 with mutation K6a c.541-2A>G. The resulting cDNA was amplified by PCR and cloned, and several clones were sequenced to identify the consequence of this mutation.…”

“…In all cases, the mutations were heterozygous sequence changesmissense, nonsense, small deletion/insertion or splice-site mutations -confirming this is predominantly, if not exclusively, an autosomal dominant disorder. While there are a few case reports of recessive PC reported in the literature, 19 as yet there are no recessive cases with confirmed genetic testing. The majority of the mutations identified have been previously reported with some mutations, for example K6a p.Asn172del, K16 p.Asn125Ser, K16 p.Arg127Cys and K17 p.Asn92Ser occurring frequently.…”

The molecular genetic analysis of the expanding pachyonychia congenita case collection

“…Splice-site mutations were found in six families in KRT6A. In five of these (families [16][17][18][19][20] mutations were at the intron 1/exon 2 boundary of K6a; three different sequence changes were identified, all of which we have reported previously, 16 but at that time, owing to the unavailability of mRNA, we were unable to identify the mutations at the protein level. However, in this study we obtained mRNA from a skin biopsy from an affected individual from family 17 with mutation K6a c.541-2A>G. The resulting cDNA was amplified by PCR and cloned, and several clones were sequenced to identify the consequence of this mutation.…”

Clinical and Pathological Features of Pachyonychia Congenita

“…General clinical characteristics Among PC cases identified from the literature, IPCRR, or NRIRD, all but three cases in two unrelated families (Chong-Hai and Rajagopalan, 1977;Haber and Rose, 1986) are consistent with an autosomal dominant pattern of inheritance. One of these two reports bases the claim of recessive inheritance upon parental consanguinity plus the fact that no other family members exhibited the disease (Chong-Hai and Rajagopalan, 1977); however, it is more likely that this case represented a spontaneous dominant mutation rather than recessive inheritance.…”

“…One of these two reports bases the claim of recessive inheritance upon parental consanguinity plus the fact that no other family members exhibited the disease (Chong-Hai and Rajagopalan, 1977); however, it is more likely that this case represented a spontaneous dominant mutation rather than recessive inheritance. In the other possible recessive family, there were two affected offspring born to consanguineous parents (Haber and Rose, 1986); however, this could also be explained by one parent carrying a dominant mutation as a gonadal mosaic. In fact, the rate of spontaneous mutation appears to be relatively high, with 85 of 294 cases (29%) from the literature reporting a negative family history.…”