OBJECTIVE: To determine whether NR5A1 (SF-1) variants are a cause of primary ovarian insufficiency (POI) in 26 young women with similar genetic background. DESIGN: Genetic and functional mutation study. SETTING: University hospitals. PATIENT(S): Genetic analysis of the NR5A1 gene in 26 XX girls with POI. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): NR5A1 molecular and functional analysis. RESULT(S): Genetic analysis revealed a new c.763C>T (p.Arg255Cys) mutation and a recurrent c.437G>C (p.Gly146Ala) variant. Functional analysis of the p.Arg255Cys mutant showed a marked decrease in transactivation on the Cyp11a1 and Amh promoters. The p.Gly146Ala variant was identified significantly more often in the patients (46.1%) than in ancestry-matched control subjects (10%). CONCLUSION(S): We identified one new NR5A1 mutation in a patient of our POI cohort (prevalence 3.8%). Moreover, although our study is limited in the number of cases, we report the high frequency of the p.Gly146Ala variant in this cohort compared with the ancestry-matched control subjects. This work highlights the important role of SF-1 in ovarian function.
OBJECTIVE: To determine whether NR5A1 (SF-1) variants are a cause of primary ovarian insufficiency (POI) in 26 young women with similar genetic background. DESIGN: Genetic and functional mutation study. SETTING: University hospitals. PATIENT(S): Genetic analysis of the NR5A1 gene in 26 XX girls with POI. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): NR5A1 molecular and functional analysis. RESULT(S): Genetic analysis revealed a new c.763C>T (p.Arg255Cys) mutation and a recurrent c.437G>C (p.Gly146Ala) variant. Functional analysis of the p.Arg255Cys mutant showed a marked decrease in transactivation on the Cyp11a1 and Amh promoters. The p.Gly146Ala variant was identified significantly more often in the patients (46.1%) than in ancestry-matched control subjects (10%). CONCLUSION(S): We identified one new NR5A1 mutation in a patient of our POI cohort (prevalence 3.8%). Moreover, although our study is limited in the number of cases, we report the high frequency of the p.Gly146Ala variant in this cohort compared with the ancestry-matched control subjects. This work highlights the important role of SF-1 in ovarian function.
Authors: Raymond D Blind; Elena P Sablin; Kristopher M Kuchenbecker; Hsiu-Ju Chiu; Ashley M Deacon; Debanu Das; Robert J Fletterick; Holly A Ingraham Journal: Proc Natl Acad Sci U S A Date: 2014-10-06 Impact factor: 11.205
Authors: Helena Campos Fabbri; Juliana Gabriel Ribeiro de Andrade; Fernanda Caroline Soardi; Flávia Leme de Calais; Reginaldo José Petroli; Andréa Trevas Maciel-Guerra; Gil Guerra-Júnior; Maricilda Palandi de Mello Journal: BMC Med Genet Date: 2014-01-10 Impact factor: 2.103
Authors: Ismael Henarejos-Castillo; Alejandro Aleman; Begoña Martinez-Montoro; Francisco Javier Gracia-Aznárez; Patricia Sebastian-Leon; Monica Romeu; Jose Remohi; Ana Patiño-Garcia; Pedro Royo; Gorka Alkorta-Aranburu; Patricia Diaz-Gimeno Journal: J Pers Med Date: 2021-06-27