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PLA2G6 gene mutation and infantile neuroaxonal degeneration; report of three cases from Iran
Reza Jafarzadeh Esfehani1,2, Atieh Eslahi2,3, Mehran Beiraghi Toosi4
1Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Insights
Three novel genetic variants in the PLA2G6 gene were identified in Iranian patients with infantile neuroaxonal degeneration (INAD). This highlights the importance of advanced genetic testing for diagnosing rare neurodegenerative disorders.
Area of Science:
- Genetics
- Neuroscience
- Rare Diseases
Background:
- Infantile neuroaxonal degeneration (INAD) is a rare, progressive neurodegenerative disorder.
- INAD is a subgroup of neurodegeneration with brain iron accumulation (NBIA) disorders.
- Patients often present with developmental delay, psychomotor regression, and neurological deficits.
Purpose of the Study:
- To identify genetic variants in patients diagnosed with INAD.
- To characterize novel variants in the PLA2G6 gene.
- To emphasize the role of Whole-Exome Sequencing (WES) in diagnosing rare diseases.
Main Methods:
- Evaluated 3 pediatric patients with INAD phenotypes using Whole-Exome Sequencing (WES).
- Performed Sanger sequencing for variant co-segregation analysis within families.
- Conducted in-silico studies to determine the molecular function of identified PLA2G6 variants.
Main Results:
- Identified three novel genetic variants in the PLA2G6 gene: one homozygous missense, one splicing, and one frameshift variant.
- These variants were not previously reported in scientific literature or population databases.
- In-silico analyses indicated the potential pathogenicity of these novel variants.
Conclusions:
- Reported novel PLA2G6 gene variants in the Iranian population with INAD.
- Underscored the significance of high-throughput genetic testing for diagnosing rare diseases.
- Highlighted the utility of WES in identifying genetic causes of INAD.
Objectives:
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.
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