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Updated: May 16, 2025
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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
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Pathogenic variants identification in primary congenital glaucoma patients using whole exome sequencing
Shahzad Ahmad1, Muhammad Saleem Gandapur2, Musharraf Jelani3
1Department of Molecular Biology & Genetics, Institute of Basic Medical Sciences, Khyber Medical University, Phase V, Hayatabad, Peshawar, 25000, Khyber Pakhtunkhwa, Pakistan.
Scientific Reports
|April 1, 2025
Summary
Genetic analysis of Primary Congenital Glaucoma (PCG) in Pashtun families identified novel CYP1B1 mutations. This research enhances understanding of PCG
Area of Science:
- Ophthalmology
- Genetics
- Human Molecular Genetics
Background:
- Primary Congenital Glaucoma (PCG) is a severe inherited condition causing vision impairment in infants and children.
- The genetic underpinnings of PCG, especially in consanguineous populations like the Pashtun community, remain incompletely understood.
Purpose of the Study:
- To investigate the genetic basis of PCG in six consanguineous Pashtun families using whole exome sequencing.
- To identify pathogenic variants in known PCG-related genes, with a focus on CYP1B1.
Main Methods:
- Whole exome sequencing was performed on six Pashtun families affected by PCG.
- A variant prioritization strategy focused on CYP1B1, followed by Sanger sequencing for validation and segregation analysis.
Main Results:
- Four pathogenic homozygous variants in CYP1B1 were identified across the six families.
- A novel homozygous mutation (c.9delC) was found in one family, and a previously unreported variant (c.1168C>A) in two families.
- Known mutations and a polymorphism in CYP1B1 were also detected, confirming its role in PCG.
Conclusions:
- Novel pathogenic CYP1B1 variants contribute to PCG in consanguineous Pashtun populations.
- This study deepens the understanding of PCG genetics and supports genetic counseling and early intervention.
- The findings underscore the importance of genetic studies in specific ethnic groups for rare diseases.
