Objective: To investigate the underlying pathogenic variants in four consanguineous Pakistani families segregating Ataxia with Oculomotor Apraxia type 1

Background: Ataxia with Oculomotor Apraxia type 1 (AOA1, MIM 208920) is a rare disorder characterized by early-onset progressive cerebellar ataxia, oculomotor apraxia, choreodystonia and sensorimotor peripheral polyneuropathy. It is caused by biallelic variants in  APTX  that encodes for Aprataxin protein. Aprataxin plays an important role in the DNA single strand break repair mechanism. To date, more than 40 APTX variants associated with AOA1 have been identified, including missense, nonsense, frame shift, splice site variants and also the complete deletion of APTX. 

Method: In this study, whole exome sequencing (WES)  was performed on probands to identify the disease causing variants. Sanger sequencing was used for co-segregation analysis of the variants in the family.

Results: This study identified one novel (c.1004A>G p.(His335Arg)) and three previously reported pathogenic APTX variants in four unrelated consanguineous Pakistani families, segregating AOA1 in an autosomal recessive manner. The three variants were already reported in the literature but these patients are the very first to be reported in Pakistan.

Conclusion: The findings of the study enhance the genotypic spectrum of the APTX associated AOA1 ataxia, expand the geographic distribution of the gene and also emphasize the use of WES as a powerful diagnostic tool.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/whole-exome-sequencing-identifies-novel-variants-underlying-ataxia-with-oculomotor-apraxia-type-1-in-pakistani-consanguineous-families/