OBJECTIVE: The goal of this study was to determine whether mutations of meiotic genes, such as disrupted meiotic cDNA (DMC1), MutS homolog (MSH4), MSH5, and S. cerevisiae homolog (SPO11), were associated with premature ovarian failure (POF). DESIGN: Case-control study. METHODS: Blood sampling, karyotype, hormonal dosage, ultrasound, and ovarian biopsy were carried out on most patients. However, the main outcome measure was the sequencing of genomic DNA from peripheral blood samples of 41 women with POF and 36 fertile women (controls). RESULTS: A single heterozygous missense mutation, substitution of a cytosine residue with thymidine in exon 2 of MSH5, was found in two Caucasian women in whom POF developed at 18 and 36 years of age. This mutation resulted in replacement of a non-polar amino acid (proline) with a polar amino acid (serine) at position 29 (P29S). Neither 36 control women nor 39 other patients with POF possessed this genetic perturbation. Another POF patient of African origin showed a homozygous nucleotide change in the tenth of DMC1 gene that led to an alteration of the amino acid composition of the protein (M200V). CONCLUSIONS: The symptoms of infertility observed in the DMC1 homozygote mutation carrier and in both patients with a heterozygous substitution in exon 2 of the MSH5 gene provide indirect evidence of the role of genes involved in meiotic recombination in the regulation of ovarian function. MSH5 and DMC1 mutations may be one explanation for POF, albeit uncommon.
OBJECTIVE: The goal of this study was to determine whether mutations of meiotic genes, such as disrupted meiotic cDNA (DMC1), MutS homolog (MSH4), MSH5, and S. cerevisiae homolog (SPO11), were associated with premature ovarian failure (POF). DESIGN: Case-control study. METHODS: Blood sampling, karyotype, hormonal dosage, ultrasound, and ovarian biopsy were carried out on most patients. However, the main outcome measure was the sequencing of genomic DNA from peripheral blood samples of 41 women with POF and 36 fertile women (controls). RESULTS: A single heterozygous missense mutation, substitution of a cytosine residue with thymidine in exon 2 of MSH5, was found in two Caucasian women in whom POF developed at 18 and 36 years of age. This mutation resulted in replacement of a non-polar amino acid (proline) with a polar amino acid (serine) at position 29 (P29S). Neither 36 control women nor 39 other patients with POF possessed this genetic perturbation. Another POFpatient of African origin showed a homozygous nucleotide change in the tenth of DMC1 gene that led to an alteration of the amino acid composition of the protein (M200V). CONCLUSIONS: The symptoms of infertility observed in the DMC1 homozygote mutation carrier and in both patients with a heterozygous substitution in exon 2 of the MSH5 gene provide indirect evidence of the role of genes involved in meiotic recombination in the regulation of ovarian function. MSH5 and DMC1 mutations may be one explanation for POF, albeit uncommon.
Authors: Michelle A Wood-Trageser; Fatih Gurbuz; Svetlana A Yatsenko; Elizabeth P Jeffries; L Damla Kotan; Urvashi Surti; Deborah M Ketterer; Jelena Matic; Jacqueline Chipkin; Huaiyang Jiang; Michael A Trakselis; A Kemal Topaloglu; Aleksandar Rajkovic Journal: Am J Hum Genet Date: 2014-12-04 Impact factor: 11.025
Authors: Yali Xue; Yuan Chen; Qasim Ayub; Ni Huang; Edward V Ball; Matthew Mort; Andrew D Phillips; Katy Shaw; Peter D Stenson; David N Cooper; Chris Tyler-Smith Journal: Am J Hum Genet Date: 2012-12-07 Impact factor: 11.025
Authors: Sandrine Caburet; Valerie A Arboleda; Elena Llano; Paul A Overbeek; Jose Luis Barbero; Kazuhiro Oka; Wilbur Harrison; Daniel Vaiman; Ziva Ben-Neriah; Ignacio García-Tuñón; Marc Fellous; Alberto M Pendás; Reiner A Veitia; Eric Vilain Journal: N Engl J Med Date: 2014-03-06 Impact factor: 91.245