PLA2G6 gene mutation and infantile neuroaxonal degeneration; report of three cases from Iran

Document Type : Original Article

Authors

1 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Paediatric Neurology, Ghaem Medical Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad

5 Iranian Academic Center for Education, Culture and Research, (ACECR), Mashhad, Iran

Abstract

Objective(s): Infantile neuroaxonal degeneration (INAD) is a rare subgroup of neurodegeneration with brain iron accumulation (NBIA) disorders. This progressive disorder may develop during the early years of life. Affected individuals mostly manifest developmental delay and/or psychomotor regression as well as other neurological deficits. In the present study, we discussed 3 INAD patients diagnosed before the age of 10 by using Whole-Exome Sequencing (WES).
Materials and Methods: We evaluated 3 pediatric patients with clinical phenotypes of INAD who underwent WES. Sanger sequencing was performed for co-segregation analysis of the variants in the families. An in-silico study was conducted for identification of the molecular function of the identified genetic variants in the PLA2G6 gene.
Results: We detected three novel genetic variants in the PLA2G6 gene including a homozygous missense (NM_003560.2; c.1949T>C; p.Phe650Ser), a splicing (NM_001349864; c.1266-1G>A) and a frameshift variant (NM_003560.4; c.1547_1548dupCG; p.Gly517ArgfsTer29). Since the variants were not previously reported in literature or population databases, we performed in-silico studies for these variants and demonstrated their potential pathogenicity.
Conclusion: The current study reports novel genetic variants in the PLA2G6 gene in the Iranian population, emphasizing the importance of high-throughput genetic testing in rare diseases.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 24, Issue 9
September 2021
Pages 1190-1195

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