Novel Inactivating Mutation of the FSH Receptor in Two Siblings of Indian Origin With Premature Ovarian Failure.
J Clin Endocrinol Metab
; 100(6): 2154-7, 2015 Jun.
Article
in En
| MEDLINE
| ID: mdl-25875778
ABSTRACT
CONTEXT Inactivating FSH receptor (FSHR) mutations can affect ovarian function, resulting in variable clinical presentations ranging from primary amenorrhea to premature menopause. FSHR mutations have been largely reported in the Finnish population, but in patients of Asian Indian descent, the incidence of FSHR mutations is extremely rare. CASE DESCRIPTION Two female siblings of Indian descent were diagnosed with primary ovarian failure and hypergonadotropic hypogonadism. The daughters were the result of a consanguineous marriage between second cousins. A combination of comparative genomic hybridization plus single nucleotide polymorphism array and whole exome sequencing was conducted on the family to identify potential causative genetic variants. CONCLUSION:
Both daughters were found to have a novel pathogenic variant in FSHR (c.1253T>G, p.Ile418Ser), inherited as an autosomal recessive trait from heterozygous parents. This loss of function mutation is located in exon 10 of FSHR affecting the second transmembrane helix of the FSHR protein. The transmembrane domain of FSHR is highly conserved across species and is involved in signal transduction. The FSHR c.1253T>G variant is next to a known pathogenic variant, rs12190966 (c.1255G>A, p.Ala419Thr), previously reported in a Finnish woman with primary amenorrhea.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, FSH
/
Primary Ovarian Insufficiency
/
Mutation, Missense
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Female
/
Humans
/
Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2015
Type:
Article