Compound heterozygous ABCA12 mutations including a novel nonsense mutation underlie harlequin ichthyosis.
Recently, it has been reported that several harlequin ichthyosis (HI) patients survive the neonatal period and their condition subsequently improves. Here we describe a 2-year-old Japanese boy who exhibited typical clinical features of HI at birth. He survived beyond the neonatal period after oral retinoid treatment and, at the age of 2 years, showed moderately thick, lamellar scales and erythroderma over his whole body. The patient is a compound heterozygote for 2 ABCA12 mutations, a paternal deletion mutation c.2021_2022del (p.Lys674ArgfsX63) and a novel maternal nonsense mutation c.7444C --> T (p.Arg2482X). Electron microscopic observation of a skin biopsy specimen from the perinatal period revealed epidermal ultrastructural features consistent with HI. Immunofluorescence labeling using antiserum against a C-terminal ABCA12 epitope showed loss of expression in the patient's epidermis. The present patient demonstrates that rapid diagnosis of HI by ABCA12 expression analysis and mutation detection, and early commencement of systemic retinoid therapy are crucial to significantly improving an HI patient's prognosis.
Akiyama
Masashi
M
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. akiyama@med.hokudai.ac.jp
Sakai
Kaori
K
Sato
Toshihiro
T
McMillan
James R
JR
Goto
Maki
M
Sawamura
Daisuke
D
Shimizu
Hiroshi
H
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D006579:Heterozygote; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics* / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D012867:Skin / Q000473:pathology / Q000648:ultrastructure
D018528:ATP-Binding Cassette Transporters; D018389:Codon, Nonsense