Abstract
OBJECTIVE: To identify genetic causes of Shabbir syndrome in two patients of Pakistani origin. METHODS: In the present study, we have investigated a Pakistani family with two affected members segregating Laryngo-onycho-cutaneous (LOC) syndrome. The patients were diagnosed as suspected cases of LOC based on phenotypes including abnormal larynx, nails, and hyperpigmentation in patients' eyes. Genetic investigation was done by performing whole exome sequencing (WES) using DNA of the patients. Sanger sequencing was performed to validate WES findings and segregation analysis in the family. RESULTS: Data analysis of exomes and Sanger sequencing of patients revealed a homozygous one base pair duplication (NM_000227.6; LAMA3; c.151dup; p.Val51GlyfsTer4) in LAMA3 in the patients. Parents of the patients were heterozygous for the identified variant. CONCLUSION: Previously, the same variant has been found in most of the Pakistani Punjabi patients affected with LOC. Therefore, Pakistani Punjabi families affected with Shabbir Syndrome may be screened for c.151dup variant in LAMA3 using targeted sequencing. Sanger sequencing is a cost-effective and time-saving technique as compared to whole exome/genome sequencing. Hence, developing ethnicity-specific LAMA3 targeted molecular diagnostic test would be cost-effective. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.