Prevalence and carrier frequency of Canavan disease in a South Indian community with implications for research and public health

Canavan disease (CD) is a progressive leukodystrophy characterized by the spongy degeneration of white matter in the brain. Only three reports from India have been elucidated the ASPA gene mutation in patients diagnosed with CD. At our center, two genetically confirmed cases of juvenile Canavan disease have been identified. Both patients possess a novel genetic variant in the ASPA gene, c.526G > A (p. Gly176Ser), which has been classified as pathogenic. A preliminary study conducted at our centre suggested the presence of a founder effect within this population. Hence, the current study aimed to analyse the cross-sectional prevalence and carrier frequency of the disease and confirm the founder effect. Five hundred seventy-five blood samples were collected from individuals in this community after obtaining informed, written consent. The ASPA gene, specifically exon 3, was analysed utilizing an in-house developed, cost-effective allele-specific PCR approach in all samples. Three short tandem repeat (STR) markers-D17S1828, D17S919, and D17S1298-were employed to examine the founder effect of the mutation by fragment analysis. The carrier frequency in our study population was found to be 1 in 23, higher than that reported in the Jewish population. The allele-specific PCR technique proved to be sensitive and cost-effective for mass screening. All identified carriers displayed specific variations in the 23 heterozygous allelic repeats. At the same time, the affected individuals manifested homozygous alleles for the D17S1828 marker, confirming that this variant is indigenous to the population under study. The D17S919 marker (18/19 repeats) was absent in the control cohort but present in the community under investigation, further substantiating the founder effect. Furthermore, the study identified other potential genetic disorders in this community that warrant further investigation. This study underscores the critical importance of carrier screening in communities characterized by high consanguinity to mitigate the prevalence of recessive disorders in future generations. The elevated carrier frequency observed in this community relative to that in Ashkenazi Jews points to a potential underestimation of prevalence, this might be due to the limited number of community-based studies conducted on rare diseases.