ABSTRACT
The aim of this study is to determine if Müllerian agenesis has a genetic basis linked to the WNT genes. Genomic DNA analyses for mutations in the coding sequences of four members of this family in a series of 11 women with Mayer-Rokitansky-Kuster-Hauser syndrome found four variants in the coding sequence of these genes, but causal mutations were not observed. This supports the hypothesis that mutations in the coding sequence of WNT4, WNT5A, WNT7A, and WNT9B are not responsible for the Mayer-Rokitansky-Kuster-Hauser syndrome.
Subject(s)
Amenorrhea/genetics , DNA Mutational Analysis , Fallopian Tubes/abnormalities , Mullerian Ducts/abnormalities , Uterus/abnormalities , Vagina/abnormalities , Wnt Proteins/genetics , Female , Humans , Mutation/genetics , Polymorphism, Single Nucleotide/genetics , Proto-Oncogene Proteins/genetics , Syndrome , Wnt-5a Protein , Wnt4 ProteinABSTRACT
OBJECTIVE: To determine if there is a relationship between various forms of partial AZFc deletions and spermatogenic failure. DESIGN: Case-control study. SETTING: Infertility clinic (Tenon Hospital, Paris). PATIENT(S): 557 men, comprising 364 infertile men from mixed ethnic backgrounds, and 193 men with known fertility (n = 84) and/or normospermic (n = 109). INTERVENTION(S): Characterization of 32 partial AZFc deletions. MAIN OUTCOME MEASURE(S): DAZ gene cluster divided into two families (DAZ1/2 and DAZ3/4), CDY1 gene, and Y-chromosome haplogroups. RESULT(S): We observed 18 partial AZFc deletions in 364 (4.95%) infertile men compared with 14 out of 193 (7.25%) in the control normospermic/fertile group. CONCLUSION(S): The analysis of informative Y-chromosome single nucleotide variants combined with Y-chromosome haplogroup definition enabled us to infer seven deletion classes that occur on a minimum of six Y-chromosome parental architectures. We found no relationship between either the presence or the absence of DAZ1/2, DAZ3/4, CDY1a, or CDY1b with spermatogenic failure at least on one Y-chromosome lineage. The DAZ dosage and Southern blot analyses indicated that the majority of individuals tested carried two copies of the DAZ gene, indicating a partial AZFc deletion. Our data are consistent with the hypothesis that, at least in our study populations, partial AZFc deletions may have a limited impact on fertility.
