Abstract:
Neurodevelopmental disorders (NDDs) are characterized by impaired cognition and motor developmental milestones. The etiology of NDDs is heterogeneous, leading to the disruptive cognition, impaired adaptive behavior, and interrupted psychomotor and communication skills. Examples of neurodevelopmental disorders include attention deficits/hyperactivity disorder (ADHD), microcephaly, autism spectrum disorder (ASD), learning disabilities, intellectual disability (ID), Mental Retardation, Schizophrenia, conduct disorders and impairments in speech and hearing. Autosomal recessive primary microcephaly (MCPH) is characterized by a significant reduction in head circumference (-3 to -5SD) with normal architecture of brain. The objective of the study was to identify novel variants through Gene Panels via Next Generation Sequencing in the individuals affected with MCPH. Blood samples of the affected families were collected from various regions of Sothern Punjab, Pakistan. DNA was extracted by performing Salting-out method of DNA extraction. Nano-drop method of spectrophotometry and agarose gel electrophoresis was performed to evaluate the quality and quantity of DNA. Mutational analysis was done by performing gene panel sequencing for 86 candidate genes. A homozygous variant (NM_018136.4; c.9492T>G) of the ASPM gene leading to protein truncation (p.Tyr3164*) is identified in one family. A compound heterozygous nonsense variant (p.Arg3244*, p.Arg1895Lysfs*8) in exon 24 and exon 18 of the ASPM gene is also identified in one family. Furthermore, 3 families in which potential disease variants in panel genes were not identified are subjected to whole-exome sequencing. Our study enhances the mutation spectrum of MCPH and identified novel families with the potential to identify new causative gene/s responsible for MCPH phenotype. Identification of mutated genes will signify a vital pioneer step for the better understanding of molecular mechanisms controlling normal brain development and pathogenesis of neurodevelopmental disorders. Recurrence risk regarding such disorders can be better assessed via molecular diagnosis.
Page(s):
107-107
DOI:
DOI not available
Published:
Journal: Abstract Book on Global Science Technology and Management Conference, Volume: 0, Issue: 0, Year: 2023
Keywords:
Whole exome sequencing WES
,
ASPM gene
,
Gene panel Sequencing
,
Novel mutation