FEM1A is a candidate gene for polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, and is characterized by infertility, hyperandrogenism and insulin resistance in skeletal muscle. There is evidence for a PCOS gene localized to chromosome 19p13.3. The FEMIA gene maps to chromosome 19p13.3 and is highly expressed in skeletal muscle. FEMIA is a homolog of fem-1, a sex-determination gene of Caenorhabditis elegans that controls masculinization. In a pilot study of Caucasian PCOS patients from our local clinic, we found that one of these five patients exhibited a heterozygous germline missense mutation in FEM1A, designated FEM1A*H500Y. This mutation alters an amino acid conserved from human to C. elegans, and was not found in any of 198 control chromosomes. This missense allele was not found in any of a separate group of 30 PCOS patients from a different regional/ethnic background. Immunostaining of mouse ovary demonstrated that the mouse homolog of FEM1A is expressed in androgen-producing secondary interstitial cells, with a marked increase in expression after puberty, consistent with a key feature of PCOS -- ovarian hyperandrogenism. In conclusion, FEM1A should be considered a candidate gene for PCOS, and more extensive analysis of FEM1A, both coding and regulatory sequences, is warranted in patients and families with PCOS.
Maher
Joseph F
JF
G. V. (Sonny) Montgomery Veterans Affairs Medical Center and Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. joseph.maher@med.va.gov
Hines
Randall S
RS
Futterweit
Walter
W
Crawford
Shawana
S
Lu
Deyin
D
Shen
Peidong
P
Oefner
Peter
P
Kazi
Mohammed
M
Wilson
James G
JG
Subauste
Jose S
JS
Cowan
Bryan D
BD
D018797:Cell Cycle Proteins / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D005260:Female; D006801:Humans; D016366:Open Reading Frames; D010865:Pilot Projects; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D016133:Polymerase Chain Reaction
D018797:Cell Cycle Proteins; C444344:FEM1A protein, human