Objective: Present Study was focused on improving the available genetic architecture of rare movement disorders (MD) and subsequent use of this knowledge for protective measurements like carrier screening and prenatal diagnosis for MD in Pashtoon population and globally as well.

Background: Movement disorders refer to a group of neurological conditions causing voluntary or involuntary abnormalities in movements’ i.e increase or decrease, e.g Ataxia, Parkinsonism and Hallervorden-Spatz disease etc.

Method: Two big consanguineous Pashtoon families with Neurodegenerative disorders (ND) (ND24 and ND27) showing autosomal recessive mode of inheritance and having several affected births were sampled from two different geographical regions of Khyber Pakhtunkhwa, Pakistan. Two probands were selected; one from each family and detailed clinical analysis was performed for these probands which showed symptoms of ND with low IQ and movements abnormalities. STS (Single tagged sequence) marker analyses was performed for both families for mapping of homozygosity in known genes and known loci regions using a fluorescence three primer method. No linkage was observed for known genes and loci regions. Further two central loops, one of each family were subjected to Genome wide scanning (GWS) using SNP6.0 array for detection of homozygous regions.

Results: Both families showed exclusion to already reported loci and genes during STS marker analysis. GWS showed surprising results; two candidate homozygous regions were observed for ND24 while three were observed for ND27.   Interestingly, out of these candidate homozygous regions, one on chromosome 15 (chr15: 72,036,142 – 73,321,041) was observed for both families indicating resemblance in their genetic architecture.

Conclusion: Reporting of common candidate homozygous region for both families, geographically, belonging to two distant regions shows intimacy in genetic architecture of the disease in both families. This evidently signposts the outcome of consanguinity and strengthening evidence of common ancestors for Pashtoon ethnic group. Progressive molecular examination of the shared homozygous region of these two families can result in potential outcomes for explaining disease origin in the families.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-showed-resemblance-in-genetic-architecture-of-rare-movement-disorders-in-consanguineous-pashtoon-ethnic-group/