Orphanet Journal of Rare Diseases | Deafness-Infertility Syndrome Gene Carrier Frequency in the Peruvian Population

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This study is the first to analyze the carrier frequency of Deafness-Infertility Syndrome (DIS) in the Peruvian population, revealing that approximately 1.1% of individuals are carriers, and the frequency is associated with regional poverty levels. The research provides new insights into the epidemiology of rare diseases and highlights the necessity of premarital genetic screening.

 

Literature Overview
This article, titled 'Determination of carriers of deafness-infertility syndrome in Peru', published in the Orphanet Journal of Rare Diseases, reviews and summarizes the genetic characteristics and carrier frequency of Deafness-Infertility Syndrome (DIS) in the Peruvian population. The syndrome is caused by homozygous deletions of the CATSPER2 and STRC genes on chromosome 15q15.3, and presents with congenital hearing loss and male infertility. The study is based on clinical data and Chromosomal Microarray Analysis (CMA), applying Hardy-Weinberg equilibrium for frequency estimation. It also examines the distribution differences of DIS carriers across natural regions and poverty groups, finding higher carrier frequency in areas with greater poverty.

Background Knowledge
Deafness-Infertility Syndrome (DIS) is a rare genetic disorder caused by deletions in the CATSPER2 and STRC genes, characterized by congenital sensorineural hearing loss (SNHL) and male infertility. Globally, the syndrome has been identified in consanguineous families in several countries, but no systematic study has been conducted in Peru. Currently, about 6-8% of the population suffers from rare diseases, of which 80% have a genetic basis, and hearing loss is a significant contributor to learning difficulties and adult poverty. Variants in the STRC gene are associated with mild to moderate SNHL, while CATSPER2 deletions affect sperm motility, leading to male infertility. Since SNHL is often underestimated, this study emphasizes the importance of genetic testing in premarital screening to prevent disease transmission. Major challenges include limited case numbers, failure to fully meet Hardy-Weinberg equilibrium assumptions, and potential data bias.

 

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Study Design and Methods
This study employed a descriptive cross-sectional design, reviewing patient data from the National Institute of Child Health (INSN) in Peru between 2015 and 2022 who underwent Chromosomal Microarray Analysis (CMA). Patients were included if their CMA quality index met the Affymetrix® platform requirements. Cases with incomplete data or where guardians declined participation were excluded. CMA was performed using the GeneChip CytoScan 750K Array (Affymetrix®), focusing on deletions in the STRC and CATSPER2 genes. The national DIS carrier frequency was estimated using Hardy-Weinberg equilibrium, and statistical analyses were integrated with population data from INEI (National Institute of Statistics and Data Processing in Peru). The geographic origin and poverty levels of patients and their ancestors were categorized, and chi-square goodness-of-fit tests were used to assess associations between carrier frequency and region or poverty group. All analyses were conducted using STATA 15.0 and Jamovi 2.3, with statistical significance set at p < 0.05.

Key Findings and Insights

• Among 2142 patients who underwent CMA, 35 were found to carry STRC and/or CATSPER2 gene deletions, including 26 with both gene deletions and 9 with only CATSPER2 deletion.
• The study estimates that approximately 367,364 individuals in Peru are DIS carriers, with about 57,442 likely affected by the syndrome, yielding an overall carrier frequency of approximately 1.1%.
• Carrier frequency was significantly associated with regional poverty levels, with higher proportions in areas of greater poverty, particularly in Group 1 (Cajamarca) and Group 2 (Ayacucho, Huancavelica, etc.).
• About 68.6% of DIS carriers had no history of consanguinity, suggesting a higher prevalence even in non-consanguineous families.
• Carriers were predominantly concentrated in coastal areas such as Lima, and ancestral origin analysis showed higher DIS carrier frequency in Lima and Junín regions.
• The study also found that CATSPER2 deletion carriers were mainly from Lima, with uneven distribution across poverty groups.

Implications and Future Directions
This is the first study to assess the genetic carrier frequency of Deafness-Infertility Syndrome (DIS) in the Peruvian population, revealing a potential link with regional poverty levels. The findings can inform public health policies and promote premarital or prenatal genetic screening. Future studies could extend to other South American countries to verify the geographic distribution of DIS carrier frequency. Additionally, the role of STRC and CATSPER2 deletions in male infertility requires further investigation to explore potential therapeutic targets.

 

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Conclusion
This study analyzed 2142 patients in Peru who underwent CMA between 2015 and 2022, identifying 35 carriers of STRC and/or CATSPER2 deletions. It estimates that approximately 367,364 individuals in Peru are DIS carriers, with about 57,442 potentially affected. The carrier frequency is higher in regions with higher poverty levels, particularly in Cajamarca (Group 1) and Ayacucho (Group 2). Carriers were mainly concentrated in the coastal city of Lima, suggesting that premarital screening is especially important in this area. The results support the inclusion of genetic screening in public health prevention strategies, particularly in high-risk, poverty-stricken regions. However, due to reliance on medical records, there may be information bias, and the small sample size limits precise national inference. Future research should increase the sample size and explore the functional mechanisms of STRC and CATSPER2 deletions in different populations to provide more accurate genetic counseling and reproductive guidance.

 

Luana Carolina Ventura Cuellar, Kevin Bryan Aviles Jascha, and Hugo Hernan Abarca-Barriga. Determination of carriers of deafness-infertility syndrome in Peru. Orphanet Journal of Rare Diseases.