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Updates on Clinical and Genetic Heterogeneity of ASPM in 12 Autosomal Recessive Primary Microcephaly Families in Pakistani Population
- Source :
- Frontiers in Pediatrics, Vol 9 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- Microcephaly (MCPH) is a genetically heterogeneous disorder characterized by non-progressive intellectual disability, small head circumference, and small brain size compared with the age- and sex-matched population. MCPH manifests as an isolated condition or part of another clinical syndrome; so far, 25 genes have been linked with MCPH. Many of these genes are reported in Pakistani population, but due to a high rate of consanguinity, a significant proportion of MCPH cohort is yet to be explored. MCPH5 is the most frequently reported type, accounting for up to 68.75% alone in a genetically constrained population like Pakistan. In the current study, whole exome sequencing (WES) was performed on probands from 10 families sampled from South Waziristan and two families from rural areas of the Pakistani Punjab. Candidate variants were validated through Sanger sequencing in all available family members. Variant filtering andin silicoanalysis identified three known mutations inASPM, a MCPH5-associated gene. The founder mutation p.Trp1326*was segregating in 10 families, which further confirmed the evidence that it is the most prominent mutation in Pashtun ethnicity living in Pakistan and Afghanistan. Furthermore, the previously known mutations p.Arg3244*and p.Arg1019*were inherited in two families with Punjab ethnic profile. Collectively, this study added 12 more families to the mutational paradigm ofASPMand expanded the Pakistani MCPH cohort.
- Subjects :
- 0301 basic medicine
Microcephaly
Population
Consanguinity
Pediatrics
RJ1-570
whole exome sequencing
ASPM
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Medicine
education
Exome sequencing
Genetics
Sanger sequencing
education.field_of_study
Genetic heterogeneity
business.industry
primary microcephaly
Pakistani population
medicine.disease
founder effect
030104 developmental biology
MCPH5
Pediatrics, Perinatology and Child Health
symbols
business
030217 neurology & neurosurgery
Founder effect
Subjects
Details
- ISSN :
- 22962360
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pediatrics
- Accession number :
- edsair.doi.dedup.....9eba1831063bea034356e316b351d088