Genetics in medicine : official journal of the American College of Medical Genetics · 2026
Birt-Hogg-Dubé syndrome, prevalence of identified cases according to clinical indication in a cohort of 1,084 patients with genetic analysis.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hercent Agathe, Ba Ibrahima, Lamoril Jerôme, Lafitte Philippe, Diallo Karim, Mary Mickael, Chelbi Malika, Mesli Farah, Benattia Amira, Richard Stephan, Villy Marie-Charlotte, Sroussi Marine, Ingster Olivier, Bataille Pauline, Hickman Geoffroy, Berthet Pascaline, Branchaud Maud, Crestani Bruno, Borie Raphael, Kannengiesser Caroline, Tchernitchko Dimitri
Аннотация
PURPOSE: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by pathogenic variants (PVs) in the FLCN gene. This study aimed to characterize the clinical presentation of patients carrying a FLCN pathogenic variation and to identify the most indicative clinical features of the syndrome.
METHODS: We analysed clinical and molecular data from 1,084 consecutive probands with a clinical suspicion of BHD. The frequency of FLCN PVs was assessed, based on clinical presentation and family history.
RESULTS: Among the 1,084 probands analysed, 29% carried a PV in FLCN. Isolated fibrofolliculomas showed the highest diagnostic yield (55.8%, 95% CI: 44.7-66.5%), whereas isolated pulmonary cysts and renal cancer were less frequently associated with FLCN PVs (4.8%, 95% CI: 2.9-7.5% and 0.6%, 95% CI: 0.0-3.2%, respectively). Multivariable analysis identified fibrofolliculomas (OR=12.9) and pneumothorax (OR=5.8) as the strongest predictors. A family history of BHD-related symptoms increased the likelihood of detecting a FLCN PV. 244 relatives who carry the familial pathogenic variation were assessed: in the age 50-60 years group, only 60% had developed BHD-related symptoms. Finally, two patients with a mosaic FLCN PV were discovered.
CONCLUSION: Fibrofolliculomas represent the strongest predictor of FLCN pathogenic variants. The combination of clinical features significantly improves diagnostic yield, supporting a targeted genetic screening approach.
METHODS: We analysed clinical and molecular data from 1,084 consecutive probands with a clinical suspicion of BHD. The frequency of FLCN PVs was assessed, based on clinical presentation and family history.
RESULTS: Among the 1,084 probands analysed, 29% carried a PV in FLCN. Isolated fibrofolliculomas showed the highest diagnostic yield (55.8%, 95% CI: 44.7-66.5%), whereas isolated pulmonary cysts and renal cancer were less frequently associated with FLCN PVs (4.8%, 95% CI: 2.9-7.5% and 0.6%, 95% CI: 0.0-3.2%, respectively). Multivariable analysis identified fibrofolliculomas (OR=12.9) and pneumothorax (OR=5.8) as the strongest predictors. A family history of BHD-related symptoms increased the likelihood of detecting a FLCN PV. 244 relatives who carry the familial pathogenic variation were assessed: in the age 50-60 years group, only 60% had developed BHD-related symptoms. Finally, two patients with a mosaic FLCN PV were discovered.
CONCLUSION: Fibrofolliculomas represent the strongest predictor of FLCN pathogenic variants. The combination of clinical features significantly improves diagnostic yield, supporting a targeted genetic screening approach.