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Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) is a well-known malformation pattern of the Mullerian ducts (MDs) characterized by congenital absence of the uterus and vagina. To date, most cases remain unexplained at molecular level. As female Wnt9b-/- mice show a MRKHS-like phenotype, WNT9B has emerged as a promising candidate gene for this disease. We performed retrospective sequence analyses of WNT9B in 226 female patients with disorders of the MDs, including 109 patients with MRKHS, as well as in 135 controls. One nonsense mutation and five likely pathogenic missense mutations were detected in WNT9B. Five of these mutations were found in cases with MRKHS accounting for 4.6% of the patients with this phenotype. No pathogenic mutations were detected in the control group (p = 0.017). Interestingly, all of the MRKHS patients with a WNT9B mutation were classified as MRKHS type 1, representing 8.5% of the cases from this subgroup. In previous studies, two of the patients with a WNT9B mutation were found to carry either an additional deletion of LHX1 or a missense mutation in TBX6. We conclude that mutations in WNT9B were frequently associated with MRKHS in our cohort and some cases may be explained by a digenic disease model.

Background and Objectives Standard treatments of high-grade Cervical intraepithelial neoplasia (CIN) are conisation procedures. Theses methods have proven effectiveness but are associated with an increased risk of subsequent pregnancy complications. Recently, photodynamic therapy (PDT) of CIN using hexylaminolevulinate (HAL) may represent an alternative treatment without the risk of cervical insufficiency or scaring. This study aims to evaluate the economical aspect of CIN treatment including associated pregnancy complications by comparing both methods. Materials and Methods We developed model treatment pathways for both conisation procedures and PDT using HAL. Thereafter, we calculated total costs for both treatment pathways including necessary re-treatments or alternative treatments. The estimated impact of conisation-related cervical insufficiency, prematurity, perinatal morbidity and life-long disability were determined. The total additional costs per conisation due to perinatal morbidity were calculated. Results The total cost of treatment for CIN with a conisation procedure alone was 1,473€, whereas the PDT procedure alone accounted for 1,386€, based of assumptions of a 50% re-PDT rate, a 70% response rate and costs of 500€ for the PDT intervention itself. We computed 71, 144 and 545 newborns born prematurely due to conisation procedures

Objective (1) To validate the mixture model in a single operator dataset and (2) to compare the detection rates for fetal chromosomal defects obtained from the mixture model with those obtained from either the delta nuchal translucency (NT) or log multiple of the median (MoM) approach. Methods Database query, viable singletons [crown-rump length (CRL) 45–84 mm corresponding to 11–13+6 weeks], December 1997 to November 2006, examined by Adam Gasiorek-Wiens, the statistical mixture model was applied. Results Seventy-four of 4171 were lost to follow-up (1.8%), 4097 singleton pregnancies included trisomy 21 (n = 34, 0.8%), trisomy 18 (n = 20, 0.5%), trisomy 13 (n = 8, 0.2%), Turner syndrome (n = 9, 0.2%) and other chromosomal abnormalities (n = 14, 0.3%). The main findings are that (1) the log-transformed NT measurements follow a mixture of two Gaussian distributions and (2) the criteria to apply either the delta-NT or log MoM models are not met. In the normal group, the majority of NT measurements were dependent on the CRL, a small group showed a median independent of the CRL. In the abnormal group it was the opposite. For a 5% false-positive rate (FPR), the trisomy 21 detection rate was 83%. Conclusions The use of the mixture model in a single operator dataset produces results compatible with the original study. The mixture model has thus been validated. Copyright © 2010 John Wiley & Sons, Ltd.