Delayed-onset pachyonychia congenita associated with a novel mutation in the central 2B domain of keratin 16

Abstract

A young girl with clinical features of pachyonychia congenita type 1 was unusual in that the typical skin and nail changes were not noted until the age of 6 years. Direct sequencing of the KRT16A gene, encoding keratin K16, revealed a novel mutation K354N in the central 2B domain of the K16 polypeptide. The mutation created a new BsmI restriction site and therefore, the mutation was confirmed in the patient and excluded from both parents and 50 normal, unrelated individuals by BsmI digestion of KRT16A polymerase chain reaction products. This is the first time a mutation has been described in this location in a keratin other than K14, where similar mutations cause the milder Weber-Cockayne and/or Köbner types of epidermolysis bullosa simplex.

The molecular basis of human keratin disorders

“…In K16, the majority of mutations are located in HIP and p.Asn125Ser is the most frequently reported mutation. In the 2B domain, only one missense mutation, p.Lys354Asn, has been reported in a girl with a delayed onset of the clinical signs of PC-1 (Connors et al 2001). Certain K16 mutations have been reported to cause FNEPPK focal keratoderma without nail changes or other features of PC-1 including missense mutations in the HIM (p.Asn125Ser, p.Arg127Cys) and a complex 14 bp deletion in the HTM (Shamsher et al 1995;Smith et al 2000).…”

Citoqueratinas

“…Na do tipo 1, caracterizada pela alteração ungueal mais hiperqueratose palmoplantar e leucoderma oral, foram detectadas mutações das CQ 6a e 16, encontradas nessas regiões. 31,32 Na do tipo 2, além do engrossamento da lâmina ungueal, ocorrem cistos na puberdade, sendo muitas vezes difícil diferenciar os subtipos na infância. 31 Nessa variante foram descritas mutações na CQ 17 33,34 e posteriormente em uma família na CQ 6b.…”

Generalized granuloma annulare after bacillus Calmette–Guérin vaccination, clinically resembling papular tuberculid

“…Traumatic neuromas can occur at any site where injury has occurred, resulting in the disorganized growth of the damaged proximal nerve as it fails to reconnect with the distal nerve sheath. 3 In histopathological findings, traumatic neuroma has been found to consist of peripheral nerve fiber proliferating to form variable-sized nerve fascicles in an irregularly arranged pattern. It is well circumscribed by surrounding fibrous tissue.…”

“…The patients listed above had delayed-onset PC, the milder phenotypes, and their mutation located at the less critical site of the keratins which is consistent with Connors et al and Xiao et al's speculation. 3,4 In conclusion, we reported a Chinese female affected with delayed-onset PC-2 caused by a novel mutation in the K6b V2 domain. The more PC patients that are reported, the more clinical data is accumulated.…”

“…2,3 However, its pathogenesis has been poorly understood. Dahl et al 4 theorized that GGA may be an immune-mediated type III reaction showing vessel changes and the presence of circulating immune complexes.…”