2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Clinical Whole Genome Sequencing for a Highly Consanguineous Population in Low-Resource Settings-Experience from an Academic Medical Center in Pakistan

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This study focuses on the use of Clinical Whole Genome Sequencing (cWGS) in a low-resource setting, specifically in a highly consanguineous population in Pakistan. The study was conducted at the Aga Khan University Hospital in Karachi, and a retrospective chart review was performed on patients seen in the Genetics Clinic between April 2022 and September 2022.<br /><br />The cWGS was ordered for 60 patients, including 58 affected pediatric patients and two unaffected females with a history of recurrent miscarriages and/or neonatal deaths. Approximately 57% of these patients belonged to consanguineous families. The majority of the index patients (85%) presented with abnormalities of the nervous system, such as global developmental delay, seizures, encephalopathy, and intellectual disability.<br /><br />Out of the patients with a diagnosis, 68% had an autosomal recessive condition, 30% had an autosomal dominant condition, and 2% had an X-linked condition. The study reported a diagnostic yield of 66% after analyzing a wide spectrum of phenotypes spanning across 39 genes.<br /><br />In addition to the diagnostic findings, three patients also had preventive findings for dilated cardiomyopathy and hereditary breast and ovarian cancer. Furthermore, each patient on average was found to be a carrier for two additional autosomal recessive conditions.<br /><br />The study concludes that cWGS is emerging as a superior sequencing modality compared to panel and Whole Exome Sequencing testing. The clinical utility of cWGS in neurological phenotypes, specifically in the under-represented Pakistani population, is comparable to previous findings. As sequencing platforms and analysis pipelines continue to improve and databases include better representation of under-represented ethnicities, it is anticipated that the diagnostic yield of cWGS will further improve.<br /><br />Overall, this study highlights the potential of cWGS in improving diagnosis rates for monogenic disorders in low-resource settings with highly consanguineous populations.

Asset Subtitle

Presenting Author - Fizza Akbar, BSc, MSc; Co-Author - Arif Mehboobali, Mr., MBA; Co-Author - Zohra Hasan, Ms, MSc.; Co-Author - Sidra Kaleem, Dr., MBBS; Co-Author - Shahnaz Ibrahim, Dr., MBBS; Co-Author - Salman Kirmani, Dr., MBBS, FACMG;

Meta Tag

Clinical History

Cognitive Disorders

Congenital Anomaly

Genetic Diversity

Genetic Testing

Genome sequencing

Genotype-Phenotype Correlations

Inheritance Patterns

Intellectual disability

Neuroscience

NextGen Sequencing

Phenotype

Triplet and Other Repeats

Co-Author Arif Mehboobali, Mr., MBA

Co-Author Zohra Hasan, Ms, MSc.

Co-Author Sidra Kaleem, Dr., MBBS

Co-Author Shahnaz Ibrahim, Dr., MBBS

Co-Author Salman Kirmani, Dr., MBBS, FACMG

Presenting Author Fizza Akbar, BSc, MSc

Keywords

Clinical Whole Genome Sequencing

low-resource setting

consanguineous population

Pakistan

nervous system abnormalities

diagnostic yield

autosomal recessive condition

autosomal dominant condition

X-linked condition

monogenic disorders