Institut Jacques Monod, Université Denis Diderot, CNRS UMR7592, Paris, France.
PLoS One. 2012;7(3):e33412. doi: 10.1371/journal.pone.0033412. Epub 2012 Mar 13.
The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10-15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients.
METHODOLOGY/PRINCIPAL FINDINGS: We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LOD(max) of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations.
CONCLUSIONS/SIGNIFICANCE: We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function.
被称为卵巢早衰（POF）的人类状况表现为 40 岁之前卵巢功能丧失。大多数 POF 病例是散发性的，但 10-15%是家族性的，表明疾病有遗传起源。尽管已经确定了几个因果突变，但大约 90%的患者的 POF 病因仍不清楚。
方法/主要发现：我们报告了一个在一个大型中东血缘关系 POF 受影响家庭中的全基因组连锁和纯合性分析，该家庭呈现常染色体隐性遗传模式。我们在染色体 7p21.1-15.3 和 7q21.3-22.2 上确定了两个具有 3.26 的 LOD(max)的区域，通过纯合性作图支持其为候选区域。对包含在最大区域内的三个候选基因（DLX5、DLX6 和 DSS1）的编码外显子和已知调控序列进行测序，未发现任何因果突变。
结论/意义：我们在人类染色体 7 上检测到两个新的与 POF 相关的基因座，为鉴定参与卵巢发育和功能控制的新基因开辟了道路。
