Orphanet Journal of Rare Diseases | Carrier Frequency Analysis of Deafness-Infertility Syndrome 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, finding that approximately 1.1% of individuals are carriers, and this 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
The article entitled 'Determination of carriers of deafness-infertility syndrome in Peru', published in the Orphanet Journal of Rare Diseases, reviews and summarizes a 2025 study analyzing 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 is characterized by congenital hearing loss and male infertility. The study is based on clinical data and Chromosomal Microarray Analysis (CMA), with frequency estimation conducted using Hardy-Weinberg equilibrium. It also analyzes the distribution differences of DIS carriers across natural regions and poverty groups, revealing higher carrier frequency among populations from regions with higher poverty levels.

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 across multiple countries, but no systematic study has been conducted in Peru. Currently, approximately 6-8% of the global population suffers from rare diseases, of which 80% have a genetic basis. Hearing loss is a significant factor contributing to learning difficulties and poverty in adulthood. Variants in the STRC gene are associated with mild to moderate SNHL, while CATSPER2 deletions affect sperm motility, leading to male infertility. Given that SNHL is often underestimated, this study emphasizes the importance of genetic testing in premarital screening to prevent transmission of genetic diseases. Challenges include limited case numbers, failure to fully satisfy Hardy-Weinberg equilibrium assumptions, and potential data bias. The significance of the study lies in providing a preliminary estimate of DIS carrier frequency in Peru and proposing screening recommendations based on geography and poverty levels.

 

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Research Methods and Experiments
The study employed a descriptive cross-sectional design, reviewing patient data from the Instituto Nacional de Salud del Niño (INSN) in Peru who underwent Chromosomal Microarray Analysis (CMA) between 2015 and 2022. Patients were included if their CMA quality index met the requirements of the Affymetrix® platform. Cases with incomplete data or where guardians refused participation were excluded. CMA was performed using the GeneChip CytoScan 750K Array (Affymetrix®) to analyze deletions in the STRC and CATSPER2 genes. National DIS carrier frequency was estimated using Hardy-Weinberg equilibrium, and statistical analysis was performed in conjunction with population data from INEI (Peru’s national statistics institute). The geographic origins and poverty levels of patients and their ancestors were categorized, and chi-square goodness-of-fit tests were used to analyze the association between carrier frequency and geographic regions or poverty groups. All statistical 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 identified as carriers of STRC and/or CATSPER2 deletions, with 26 carrying both gene deletions and 9 carrying only CATSPER2 deletions.
• The study estimates that approximately 367,364 individuals in Peru carry DIS, and about 57,442 may be affected, with a carrier frequency of approximately 1.1%.
• Carrier frequency was significantly associated with regional poverty levels, with higher proportions of carriers found in regions with higher poverty, particularly in Group 1 (Cajamarca) and Group 2 (Ayacucho, Huancavelica, etc.).
• About 68.6% of DIS carriers had no history of consanguineous marriage, indicating that the syndrome may also occur at a high frequency in non-consanguineous families.
• Carriers were predominantly concentrated in coastal areas (e.g., Lima), and ancestral origin analysis revealed higher DIS carrier frequency in Lima and Junín regions.
• The study also found that CATSPER2 deletion carriers were mainly from Lima and showed uneven distribution across multiple poverty groups.

Research Implications and Future Directions
This study is the first to evaluate the genetic carrier frequency of Deafness-Infertility Syndrome (DIS) in the Peruvian population and reveals a potential association with regional poverty levels. The findings can inform public health policies and promote premarital or pre-pregnancy genetic screening. Future studies may expand to other South American countries to verify the geographic distribution of DIS carrier frequency. In addition, further research is needed on the roles of STRC and CATSPER2 deletions in male infertility to explore potential therapeutic targets.

 

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Conclusion
This study analyzed data from 2142 patients in Peru who underwent CMA testing between 2015 and 2022, identifying 35 carriers of STRC and/or CATSPER2 deletions. The estimated number of DIS carriers in Peru is approximately 367,364, with around 57,442 individuals potentially affected. Higher carrier frequency was observed in regions with higher poverty levels, particularly in Cajamarca (Group 1) and Ayacucho (Group 2). Carriers were mainly concentrated in coastal cities like Lima, suggesting the importance of premarital screening in this region. These findings support the inclusion of genetic screening in public health prevention strategies, especially in high-risk impoverished areas. Due to the study's reliance on medical records, potential information bias and limited sample size restrict precise national inference. Future research should expand 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.