Prenatal Molecular Diagnosis of Fetal Sample

Abstract

Purpose: : Prenatal molecular diagnosis and genetic counseling of a family having Oculocutaneous Albinism type I (OCA I) disease by analyzing the inheritance and incidence of tyrosinase mutant-R239W in fetal sample. The structural properties of human tyrosinase were studied for wild and mutant type (R239W) by comparing the predicted models.

Methods: : Genomic DNA was extracted with peripheral blood samples recruited from the family members and Chorionic Villus Sample (CVS) were collected from the mother during her 3rd month of pregnancy by invasive method. PCR and bi-directional DNA sequence analysis were performed by using ABI 3130 Genetic Analyzer. Human tyrosinase structural model for the wild type and R239W mutant were predicted using Schrodinger 2011, LLC software. Accuracy of the predicted 3D structure was also validated by Ramachandran plot. These models were used to predict the effects of R239W mutant to compare with wild type of TYR gene structure.

Results: : One reported mutation Arg239Trp (p.R239W/c.715 C>T) were detected in proband; both father and mother were carrier for this mutation. Molecular prenatal diagnosis of fetal CVS sample revealed normal sequencing pattern for the mutant Arg239Trp. The pregnancy progressed precisely and delivered to a normal outcome without any phenotypic or genotypic abnormalities as per the earlier prediction of fetal sample by molecular diagnosis. The wild and mutant structures were analyzed, compared for protein stability and physico-chemical properties of TYR structure.

Conclusions: : This study addressed to the outcome of research application to the society with a basic diagnostic method. These results present, the scientific evidence by molecular prenatal diagnosis performed with OCA type 1 family. This is the first successful report revealed the profile of biological information by genetics as well as computational based approach for R239W mutant in the fetus of Indian familial case.

Keywords: gene screening • genetics • mutations