We have identified a previously unreported homozygous nonsense mutation p.Cys427X in the keratin 10 (K10) gene (KRT10) in a Turkish girl with recessive bullous congenital ichthyosiform erythroderma (BCIE) showing superficial blistering. p.Cys427X is located upstream of the previously reported homozygous truncation mutation within the same exon 6 causing mRNA decay. Immunohistochemical examination showed a complete absence of K10 protein in the patient's epidermis. The findings of this study suggest that K10 knockout patients show unique clinicopathological features of clinically mild BCIE with blisters occurring within the granular layer. In addition, the unaffected, heterozygous carriers of the mutation indicate that the K10 peptide from one normal allele alone is sufficient for keratin network formation.
Since 1994, four cases of epidermal nevus with epidermolytic hyperkeratosis (EH) caused by keratin 10 gene mutations have been reported, although no keratin 1 (K1) gene mutation has yet been reported. We detected a K1 gene (KRT1) mutation in epidermal nevus with EH in a 10-year-old Japanese male. The patient showed well-demarcated verrucous, hyperkeratotic plaques mainly on the trunk, covering 15% of the entire body surface. No hyperkeratosis was seen on the palms or soles. He had no family history of skin disorders. His lesional skin showed typical granular degeneration and, ultrastructurally, clumped keratin filaments were observed in the upper epidermis. Direct sequence analysis of genomic DNA extracted from lesional skin revealed a heterozygous 5' donor splice site mutation c.591+2T>A in KRT1. This mutation was not detected in genomic DNA samples from the patient's peripheral blood leukocytes or those of other family members. The identical splice mutation was previously reported in a family with palmoplantar keratoderma and mild ichthyosis, and was demonstrated to result in a 22 amino-acid deletion p.Val175_Lys196del in the H1 and 1A domains of K1. To our knowledge, the present patient is the first reported case of epidermal nevus associated with EH caused by a K1 gene mutation in a mosaic pattern.
The patient, a 38-year-old man with a 10-year history of deformation and pustules in his fingers and toes, presented in December 2002. Physical examination revealed tender, drumstick-like swelling in all of his fingers and toes. Erythematous, scaling, and pustular eruptions were observed on the distal area of the digits (A). The nail plates were completely destroyed. He reported having arthralgia in the distal area of the digits. Scaly erythematous and pustular eruptions were present on the forehead and right knee. Radiographs of the fingers and toes revealed remarkable bone resorption and destruction, especially in the distal phalanges (B). Histologic examination of sections of a skin lesion showed parakeratosis and neutrophils forming Munro's abscesses in the stratum corneum. Rheumatoid factor was negative. Based on the above-mentioned findings, the patient was diagnosed as having psoriatic onycho-pachydermo periostitis (POPP) combined with an axial manifestation of psoriatic arthritis. POPP was described by Fournie et al in 1989 (1). It consists of psoriatic onychodystrophy and connective tissue thickening above the distal phalanx, including a periosteal reaction. POPP can be extremely painful and frequently causes significant fuctional impairment. It has been recognized as an uncommon subset of psoriatic arthritis and, to date, only a few cases have been described (1-4). In general, POPP is regarded as a unique variant of psoriatic arthritis, but its pathology and pathophysiology are not well understood. Therapy for this rare disease is based on treatments used for psoriatic arthritis, such as sulfasalazine, methotrexate, and the anti-tumor necrosis factor antibody adalimumab (4).
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