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Penetrance is a critical parameter for assessing the disease liability of CFTR variants.
Boussaroque, A; Audrézet, M-P; Raynal, C; Sermet-Gaudelus, I; Bienvenu, T; Férec, C; Bergougnoux, A; Lopez, M; Scotet, V; Munck, A; Girodon, E.
Afiliación
  • Boussaroque A; APHP.Centre-Université de Paris, Cochin Hospital, Molecular Genetics Laboratory, Paris, France.
  • Audrézet MP; Molecular Genetics Laboratory - CHRU Brest, Brest, France; Inserm UMR 1078, GGB, F-29200 Brest, France.
  • Raynal C; Molecular Genetics Laboratory - CHU Montpellier, EA7402 Université de Montpellier, Montpellier, France.
  • Sermet-Gaudelus I; APHP.Centre Université de Paris, Necker Enfants Malades Hospital, Cystic Fibrosis Center, Paris, France and INSERM U 1151, Paris, France.
  • Bienvenu T; APHP.Centre-Université de Paris, Cochin Hospital, Molecular Genetics Laboratory, Paris, France.
  • Férec C; Molecular Genetics Laboratory - CHRU Brest, Brest, France; Inserm UMR 1078, GGB, F-29200 Brest, France.
  • Bergougnoux A; Molecular Genetics Laboratory - CHU Montpellier, EA7402 Université de Montpellier, Montpellier, France.
  • Lopez M; APHP.Centre-Université de Paris, Cochin Hospital, Molecular Genetics Laboratory, Paris, France.
  • Scotet V; Inserm UMR 1078, GGB, F-29200 Brest, France.
  • Munck A; APHP.Centre Université de Paris, Necker Enfants Malades Hospital, Cystic Fibrosis Center, Paris, France and INSERM U 1151, Paris, France; Société francaise de dépistage néonatal.
  • Girodon E; APHP.Centre-Université de Paris, Cochin Hospital, Molecular Genetics Laboratory, Paris, France. Electronic address: emmanuelle.girodon@aphp.fr.
J Cyst Fibros ; 19(6): 949-954, 2020 11.
Article en En | MEDLINE | ID: mdl-32327388
ABSTRACT

BACKGROUND:

Major issues of newborn screening (NBS) for CF are the assessment of disease liability of variants and of the penetrance of clinical CF, notably in inconclusive diagnosis. The penetrance of CF is defined as the risk of a particular genotype to lead to a CF phenotype.

METHODS:

We aimed to get insight into the penetrance of CF for fifteen CFTR variants 5 frequent CF-causing and 10 classified as of varying clinical consequence (VCC) or associated with a CFTR-related disorder (CFTR-RD) in CFTR2 or CFTR-France databases. The penetrance was approached by (1) comparison of variant allelic frequencies in CF patients (CFTR2) and in the general population; (2) estimation of the likelihood of a positive NBS test for the 14 compound heterozygous with F508del and the F508del homozygous genotypes, defined as the ratio of detected/expected number of neonates with a given genotype in the 2002-2017 period.

RESULTS:

A full penetrance was observed for severe CF-causing variants. Five variants were more frequently found in the general population than in CF patients TG11T5, TG12T5, TG13T5, L997F and R117H;T7. The likelihood of a positive NBS test was 0.03% for TG11T5, 0.3% for TG12T5, 1.9% for TG13T5, 0.6% for L997F, 11.7% for D1152H, and 17.8% for R117H;T7. Penetrance varied greatly for variants with discrepant classification between CFTR2 and CFTR-France 5.1% for R117C, 12.3% for T338I, 43.5% for D110H and 52.6% for L206W.

CONCLUSION:

These results illustrate the contribution of genetics population data to assess the disease liability of variants for diagnosis and genetic counselling purposes.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Variación Genética / Tamizaje Neonatal / Regulador de Conductancia de Transmembrana de Fibrosis Quística / Penetrancia / Fibrosis Quística Límite: Female / Humans / Male / Newborn Idioma: En Revista: J Cyst Fibros Año: 2020 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Variación Genética / Tamizaje Neonatal / Regulador de Conductancia de Transmembrana de Fibrosis Quística / Penetrancia / Fibrosis Quística Límite: Female / Humans / Male / Newborn Idioma: En Revista: J Cyst Fibros Año: 2020 Tipo del documento: Article País de afiliación: Francia