Genetics in medicine : official journal of the American College of Medical Genetics · 2007
Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data from the French-Italian HHT network.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lesca Gaëtan, Olivieri Carla, Burnichon Nelly, Pagella Fabio, Carette Marie-France, Gilbert-Dussardier Brigitte, Goizet Cyril, Roume Joelle, Rabilloud Muriel, Saurin Jean-Christophe, Cottin Vincent, Honnorat Jerome, Coulet Florence, Giraud Sophie, Calender Alain, Danesino Cesare, Buscarini Elisabetta, Plauchu Henri, French-Italian-Rendu-Osler Network
Аннотация
PURPOSE: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by arteriovenous malformations (AVM), mostly cutaneous and mucous (telangiectases), but also involving the lungs (PAVM), liver (HAVM) and brain (CAVM). We studied the relationship between the phenotype and genotype in patients with a proven mutation in either ENG (HHT1) or ACVRL1 (HHT2).
METHODS: Clinical features and their age of onset were compared between HHT1 and HHT2. The type of mutation was also analyzed. Clinical manifestations were distinguished from lesions found by screening.
RESULTS: Ninety-three HHT1 patients and 250 HHT2 patients were included. Epistaxis occurred later in HHT2, with incomplete penetrance (P<0.0001). Symptomatic PAVMs were more frequent in HHT1 (34.4 vs. 5.2%, P<0.001), as were cerebral abscesses (7.5 vs. 0.8%, P=0.002). Gastrointestinal bleeding occurred more frequently in HHT2 (16.4 vs. 6.5%, P=0.017). Symptomatic hepatic involvement was only seen in HHT2 patients. PAVMs were more frequently detected in asymptomatic HHT1 patients (54 vs. 12.8%, P<0.0001). PAVMs and HAVMs were often family clustered in HHT1 and HHT2, respectively. Truncating mutations were associated with a higher frequency of epistaxis and telangiectasis, in HHT2.
CONCLUSION: This study shows major differences between HHT1 and HHT2 phenotypes, which should be taken into account for future clinical studies.
METHODS: Clinical features and their age of onset were compared between HHT1 and HHT2. The type of mutation was also analyzed. Clinical manifestations were distinguished from lesions found by screening.
RESULTS: Ninety-three HHT1 patients and 250 HHT2 patients were included. Epistaxis occurred later in HHT2, with incomplete penetrance (P<0.0001). Symptomatic PAVMs were more frequent in HHT1 (34.4 vs. 5.2%, P<0.001), as were cerebral abscesses (7.5 vs. 0.8%, P=0.002). Gastrointestinal bleeding occurred more frequently in HHT2 (16.4 vs. 6.5%, P=0.017). Symptomatic hepatic involvement was only seen in HHT2 patients. PAVMs were more frequently detected in asymptomatic HHT1 patients (54 vs. 12.8%, P<0.0001). PAVMs and HAVMs were often family clustered in HHT1 and HHT2, respectively. Truncating mutations were associated with a higher frequency of epistaxis and telangiectasis, in HHT2.
CONCLUSION: This study shows major differences between HHT1 and HHT2 phenotypes, which should be taken into account for future clinical studies.