title: A novel MKRN3 missense mutation causing familial precocious puberty.
abstract: Central precocious puberty may be familial in about a quarter of the idiopathic cases. However, little is known about the genetic causes responsible for the disorder. In this report we describe a family with central precocious puberty associated with a mutation in the makorin RING-finger protein 3 (MKRN3) gene. A novel missense mutation (p.H420Q) in the imprinted MKRN3 gene was identified in the four affected siblings, in their unaffected father and in his affected mother. An in silico mutant MKRN3 model predicts that the mutation p.H420Q leads to reduced zinc binding and, subsequently, impaired RNA binding. These findings support the fundamental role of the MKRN3 protein in determining pubertal timing.
authors.affiliation: The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva 49202, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel liatd@clalit.org.il liatdevries@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: de Vries
authors.affiliation: The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva 49202, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel Felsentein Medical Research Center, Petah Tikva 49100, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Gat-Yablonski
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel Pediatric Endocrinology, Child Health and Sports Center, Meir Medical Center, Kfar Saba 44281, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Dror
authors.affiliation: Genetic Unit, Barzilai Medical Center, Ashkelon 78278, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Singer
authors.affiliation: The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva 49202, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Phillip
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D010375:Pedigree; D017434:Protein Structure, Tertiary; D011629:Puberty, Precocious / Q000235:genetics*; D012261:Ribonucleoproteins / Q000737:chemistry / Q000235:genetics*; D035781:Siblings; D044767:Ubiquitin-Protein Ligases
chemical_list: D012261:Ribonucleoproteins; C119425:MKRN3 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: central precocious puberty; makorin RING-finger protein 3; maternal imprinting; zinc finger