A genome-wide linkage scan in a Dutch family identifies a premature ovarian failure susceptibility locus.
Hum Reprod
; 23(12): 2835-41, 2008 Dec.
Article
in En
| MEDLINE
| ID: mdl-18689850
ABSTRACT
BACKGROUND:
Premature ovarian failure (POF) is characterized by elevated gonadotrophins and amenorrhea before the age of 40 years and occurs approximately in 1% of women. POF etiology is highly heterogeneous with a wide spectrum of etiological pathogenic mechanisms including genetic causes. These mostly involve numerical, structural or monogenic defects on the X-chromosome. Mutations in a small number of autosomal genes (such as FOXL2 and NOBOX) have been identified as a cause of POF. However, in most cases, the disease underlying mechanisms are largely unknown.METHODS:
We performed a genome-wide linkage analysis in a relatively large Dutch family with seven patients suffering from POF, showing a dominant pattern of inheritance. A genome-wide analysis, using 50K single nucleotide polymorphism arrays, was combined with conventional parametric linkage analysis.RESULTS:
We identified three genomic regions on chromosomes 5, 14 and 18 yielding suggestive linkage (multipoint LOD score of 2.4 for each region). After inclusion of one elder unaffected family member, only the region on chromosome 5 remains as a putative POF locus. In addition, we investigated a second family (three living patients over three generations) for the regions on chromosome 5, 14 and 18. Haplotype analysis supported only the locus on chromosome 5q14.1-q15.CONCLUSION:
We performed the first genome-wide linkage search in familial POF and identified a region on chromosome 5q14.1-q15, which may harbor a novel POF susceptibility gene.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Primary Ovarian Insufficiency
/
Genetic Predisposition to Disease
Type of study:
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
Hum Reprod
Journal subject:
MEDICINA REPRODUTIVA
Year:
2008
Document type:
Article
Affiliation country:
Netherlands