Novel PAX3 gene mutation in Neural Tube Defect cases in North Eastern Uttar Pradesh families

Abstract

Background: Neural Tube Defect (NTD) is a major cause of morbidity and mortality in newborns in eastern Uttar Pradesh in India. The PAX3 protein is a transcription factor expressed in early neural tube development. Neural tube defect is known to be caused by mutation in PAX3 gene which leads to functional haploinsufficiency of this gene. Methodology: The present study reports screening of 216 patients with neural defect in which 12 were familiar cases hailing from eastern Uttar Pradesh. Resequencing reveals four novel mutations in the PAX3 gene; exon 6 at 223085959_223085960insA (two families) and 223085949_223085949delA (one family) were observed and a silent mutation in PAX3 exon 1 at 223163637A>G with no amino acid chain alteration was also observed in a family. Results: The two novels non synonymous variant at 223085959_223085960insA and 223085949_223085949delA leads to frame shift mutation and the silent mutation at 223163637A>G was a synonymous mutation in PAX3 gene. The missense mutation (223085959_223085960insA) P314S showed a frequency of 0.4 and P318H (223085949_223085949delA) showed a frequency of 0.2.

Conclusion: Insilico study suggests that this mutation creates a truncated PAX3 protein resulting in its haploinsufficiency. These mutations were observed in homeodomain region of PAX3 gene which has a DNA binding activity and play important role in neural tube development.