Eastern Regional Meeting - 2008 Program & Abstracts
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Clinical, genetic, and quality of life studies of autosomal recessive congenital ichthyosis in 104 patients
S. Farasat,1 M.H. Wei,1 B. Ahvazi,1 D.J. Liewehr,1 S.M. Steinberg,1 S.J. Bale,2 P. Fleckman,3 J.R. Toro,1 ; 1. National Institutes of Health, Bethesda, MD; 2. GeneDx, Inc, Gaithersburg, MD; 3. University of Washington, Seattle, WA
Purpose of Study: Autosomal recessive congenital ichthyosis (ARCI) defines a group of clinically and genetically heterogenous disorders of keratinization. It is divided clinically into two main subtypes: lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NBCIE). Mutations in the Transglutaminase-1 (TGM1) gene have been associated with ARCI. The purpose of this investigation was to characterize the TGM1 mutation spectrum, identify novel TGM1 mutations, and study the life quality of ARCI patients.
Methods Used: One hundred and four ARCI patients were ascertained through the National Registry for Ichthyosis and Related Disorders. A questionnaire was administered during a telephone interview with participants eliciting medical history, dermatologic history, clinical, and quality of life information. Direct DNA sequencing was used to screen for mutations in TGM1.
Summary of Results: TGM1 mutations were identified in 55% (57/104) of patients. Of the 44 germline TGM1 mutations identified, 24 were novel: 9 missense, 5 nonsense, 7 frameshift, and 3 splice site. The most common mutation was IVS5-2 A>G (29 alleles). Collodion membrane at birth was reported in 60% (56/93), ectropion in 75% (78/104), eclabium in 19% (20/104), anhidrosis in 87% (90/104), alopecia in 38.5% (40/104) and plate-like scales in 77% (80/104). Patients with TGM1 mutations were significantly associated with collodion membrane at birth (p=0.006), ectropion (p=0.001), alopecia (p=0.001), and plate-like scales (p=0.005) compared with patients without TGM1 mutations. Among patients with TGM1 mutations, palm involvement was correlated with sole involvement (p=0.0001). Collodion membrane at birth was associated with ectropion (p=0.009) and eclabium (p=0.035). In patients greater than 13-years-old, 70% (38/54) reported embarrassment as a result of their skin. Among adults, 51% (27/53) felt their skin condition had impacted their career.
Conclusions: This study represents the largest investigation of ARCI and expands the spectrum of TGM1 mutations. Our results confirm that ARCI is a genetically heterogeneous disease.
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