Is germline transmission of MAD2 gene deletion associated with human fetal loss?

The spindle assembly checkpoint (SAC) monitors proper attachment of spindles to the kinetochore during mitotic and meiotic cell divisions and thus prevents aneuploidy. Chromosomal aneuploidy has been found to be associated with pregnancy loss and birth defects. Mad2 is one of the critical molecules of SAC. Deregulated Mad2 expression has been found to be associated with defective SAC-mediated abnormal meiotic progression in cell studies using animal models. Whether mutation in MAD2L1 is associated with the loss of Mad2 expression in aborted human fetuses is unknown. In this study, a correlation between aneuploidy and MAD2 defect was examined in primary fibroblast cultures obtained from abortuses. We report three trisomic abortuses with undetectable Mad2 expression. Further, quantitative real-time PCR revealed copy number deletion of MAD2 gene in these fetuses. Analysis of parental DNA samples available from two families revealed copy number loss of the same gene, suggesting Mendelian inheritance of MAD2 deletion. This germline transmission of exonic deletion of MAD2 is possibly associated with its loss of expression resulting in abnormal SAC function, subsequent aneuploidy and pregnancy loss.

Prosthetic Rehabilitation of a Maxillofacial Defect with Silicone Orbital Prosthesis: A Simplified Technique.

Rehabilitation of various maxillofacial defects is a time-consuming, complex, and overwhelming task requiring a patient-specific design and technique. Human face disfigurement involving loss of an eye enhances physical and emotional challenges. A wide range of various treatment modalities are being practiced over the period of time, with the recent one being use of ocular implants. Undoubtedly, an implant-supported orbital prosthesis has a superior outcome; it may not be as practical option considering the cost and availability, especially in economically constrained patients. The present case report describes a simplified technique for fabrication of an adhesive-retained silicone orbital prosthesis.

Role of fetal autopsy as a complementary tool to prenatal ultrasound.

AIM: To correlate and compare prenatal ultrasound with fetal autopsy examination to detect structural births defects and provide specific diagnoses. METHODS: 141 second trimester fetuses (<20 weeks and <500 g) where pregnancy was terminated for structural birth defects and/or severe intra-uterine growth restriction (IUGR) or intra-uterine death, referred to our tertiary care private, teaching hospital were examined by a team of experienced pathologist and clinical geneticist. Findings of pathology examination were compared to those provided by ultrasound examination. RESULTS: A total of 301 structural abnormalities were noted. Specific etiology was identified or syndromic diagnosis was possible in 57/141 (40.4%) cases. The maximum number of systemic anomalies (45/301, 14.95%) was noted in the central nervous system (CNS). CNS anomalies were most commonly associated with facial dysmorphism including cleft lip/palate etc. There was a complete agreement between ultrasound and autopsy findings in 41/141 (29.07%) cases, additional information that did not influence the final diagnosis and/or counseling was obtained by autopsy in 65/1416 (46.09%) cases, while additional information that influenced the final diagnosis and/or counseling was provided by autopsy in 35/141 (24.82%) cases. CONCLUSION: Fetal autopsy serves as a complementary tool to fetal ultrasound due to its ability to pick up minor anomalies and/or anomalies that were missed on ultrasound. It may be routinely performed as an attempt to reach a specific diagnosis and offer appropriate counseling to couples, following pregnancy termination for fetal anomalies.