Genetic Counseling Challenges in Interpretation of Next Generation Sequencing Results in Three Iranian Families

Genetic counseling is the process by which the patients or relatives at risk ofan inherited disorder are advised of the consequences and nature of thedisorder, the probability of developing or transmitting it, and the options opento them in management and family planning.The field of DNA sequencing is quickly moving from uses within genetic labstowards a huge number of other applications for clinical practice and humanhealth. This procedure brings a higher level of complexity in results. Manyvariations can be reported as primary findings which categorized aspathogenic, likely pathogenic, variants of uncertain significance (VUS), likelybenign and benign.There were three families undergoing whole exome sequencing. They werereferred as microcephaly, familial dysautonomia and repeated fetal hydropsfetalis respectively. Based on WES results, the variants were in accordancewith the patient s clinical presentation and confirmed in patient and herparents by sanger sequencing. The results were:1- Carpenter syndrome 2; MEGF8: NM_001410: exon 13:c. G2189A: p.R730Qand c.A2249G:p.H750R2-non-Herlitz type of junctional epidermolysis bullosa; COL17A1,NM_000494:exon 35:c.2478_2504del: P.826_835del3-Diaphanospondylodysostosis;BMPER: NM_133468: exon8: c.C664T:p.P222SThese families were undergoing prenatal diagnosis in next pregnancies. Inspite of heterozygous condition of fetuses of first and second families, theywere affected. The fetus of third family had homozygous BMPER mutation andany evidence in sequential sonographies. He was normal at birth. Accordingly,informative and supportive counselling is very important in the time of testrequest, familial making decision and prevention of legal, ethical and medicalproblems.