Jane Huang1, Hiroyuki Kondo, Eiichi Uchio. 1. Department of Ophthalmology, School of Medicine, Fukuoka University, Fukuoka, Japan. ganka@minf.med.fukuoka-u.ac.jp
Abstract
PURPOSE: Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis with approximately one-third of cases with associated ocular complications. Deletion of exons 4 to 10 of the nuclear factor kappaB essential modulator (NEMO) gene accounts for the majority of new mutations. The disease is more commonly found among Caucasians. We studied a case of an IP patient in Japan, and the genomic rearrangements. METHODS: An 11-month-old female infant exhibited the skin lesions of IP. Ocular findings were total retinal detachment with a retrolental fibrovascular mass in the right eye, and patchy retinal avascular zones and neovascularization in the left eye. The genomic rearrangement of NEMO was investigated by a polymerase chain reaction (PCR)-based diagnostic test. A skewed X-inactivation assay was also performed using the human androgen receptor gene as a genetic marker. RESULTS: Deletion of exons 4 to 10 in NEMO was detected in the proband and in other female members of her family. A complete skewing of the X-inactivation pattern causing IP was observed, indicating cells having no protection against apoptosis in response to tumor necrosis factor as the pathogenicity of the disease. CONCLUSION: This is the first case report of a Japanese female phenotype demonstrating the common genomic rearrangement in the NEMO gene.
PURPOSE:Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis with approximately one-third of cases with associated ocular complications. Deletion of exons 4 to 10 of the nuclear factor kappaB essential modulator (NEMO) gene accounts for the majority of new mutations. The disease is more commonly found among Caucasians. We studied a case of an IPpatient in Japan, and the genomic rearrangements. METHODS: An 11-month-old female infant exhibited the skin lesions of IP. Ocular findings were total retinal detachment with a retrolental fibrovascular mass in the right eye, and patchy retinal avascular zones and neovascularization in the left eye. The genomic rearrangement of NEMO was investigated by a polymerase chain reaction (PCR)-based diagnostic test. A skewed X-inactivation assay was also performed using the humanandrogen receptor gene as a genetic marker. RESULTS: Deletion of exons 4 to 10 in NEMO was detected in the proband and in other female members of her family. A complete skewing of the X-inactivation pattern causing IP was observed, indicating cells having no protection against apoptosis in response to tumor necrosis factor as the pathogenicity of the disease. CONCLUSION: This is the first case report of a Japanese female phenotype demonstrating the common genomic rearrangement in the NEMO gene.
Authors: A Smahi; G Courtois; P Vabres; S Yamaoka; S Heuertz; A Munnich; A Israël; N S Heiss; S M Klauck; P Kioschis; S Wiemann; A Poustka; T Esposito; T Bardaro; F Gianfrancesco; A Ciccodicola; M D'Urso; H Woffendin; T Jakins; D Donnai; H Stewart; S J Kenwrick; S Aradhya; T Yamagata; M Levy; R A Lewis; D L Nelson Journal: Nature Date: 2000-05-25 Impact factor: 49.962
Authors: S Aradhya; H Woffendin; T Jakins; T Bardaro; T Esposito; A Smahi; C Shaw; M Levy; A Munnich; M D'Urso; R A Lewis; S Kenwrick; D L Nelson Journal: Hum Mol Genet Date: 2001-09-15 Impact factor: 6.150