MKRN3; familial CPP; genetics of puberty; precocious puberty; Endocrinology, Diabetes and Metabolism
Abstract :
[en] ("[en] CONTEXT: Idiopathic central precocious puberty (iCPP) is defined by the premature reactivation of the hypothalamic-pituitary-gonadal axis with normal magnetic resonance imaging scan of the central nervous system, causing the development of secondary sexual characteristics before age 8 years in girls and 9 years in boys. MKRN3 loss of function variants now represent the most common genetic cause of iCPP.
OBJECTIVE: This work aims to document the clinical course of puberty in 8 families harboring pathogenic MKRN3 variants.
METHODS: This is an observational case series study of patients with CPP due to MKRN3 variants followed in a single center.
RESULTS: Genetic analysis of MKRN3 was carried out in 28 unrelated patients with iCPP and a family history of paternal inheritance or no/unavailable maternal inheritance, particularly in case of very early and rapidly evolving CPP. We identified 6 novel and 2 recently described variants in the MKRN3 gene in 9 girls, 1 boy, and their family members. These mutations were all predicted to be deleterious by in silico prediction programs.
CONCLUSION: We have identified 6 novel MKRN3 mutations in children with CPP. An MKRN3 loss of function should be considered after careful history pinpointing paternally inherited CPP. A family segregation study allowed the detection of an MKRN3 variant in 2 young brothers still prepubertal, raising the question of screening and management of asymptomatic prepubertal family members.","[en] ","")
Disciplines :
Genetics & genetic processes
Author, co-author :
Gernay, Caroline ; Paediatric Endocrinology Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, 1020 Brussels, Belgium
Brachet, Cécile; Paediatric Endocrinology Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, 1020 Brussels, Belgium
Boros, Emese; Paediatric Endocrinology Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, 1020 Brussels, Belgium
Tenoutasse, Sylvie; Paediatric Endocrinology Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, 1020 Brussels, Belgium
Libioulle, Cécile ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Heinrichs, Claudine; Paediatric Endocrinology Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, 1020 Brussels, Belgium
Language :
English
Title :
Six Novel Variants in the MKRN3 Gene Causing Central Precocious Puberty.
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