Carrier Rate of Citrullinemia, Type I in Individual Ethnic Groups Using an Expanded Carrier Test

Purpose: To identify population-specific carrier frequencies for Citrullinemia Type 1. Better knowledge of population specific carrier frequencies improves carrier testing and genetic counseling; however, prior reports have not captured data in specific ethnic groups. Identifying a fetus at risk for CTLN1 could allow prenatal planning by arranging for appropriate post-partum care to mitigate or prevent long lasting neurological damage with prompt use of metabolic therapy.

Methods: Retrospective review of 11,132 individuals who underwent expanded carrier testing utilizing a genotyping panel. The CTLN1 variants included were the common 1168G>A variant, and the rarer 421-2A>G/910C>T variant. Adjusting for the genotyping panel’s detection rate we calculated the carrier frequency for specific ethnic groups.

Results: Pan-ethnic carrier frequency of 1:383 (10*2.9/11,132), corresponding to a population prevalence of 1: 575,000. Adjusted carrier rates are: 1/124 in the Ashkenazi Jewish group; 1/392 in the Hispanic group;1/422 in the Caucasian/White group.

Conclusion: As expanded carrier testing utilization increases, it is important to continue to reassess carrier and disease frequencies of rare conditions with large ethnically diverse cohorts. This is the first report, to our knowledge, to document CTLN1 carrier rate in individual ethnic groups. This knowledge can guide preconception and prenatal counseling enabling patients and providers to identify resources and neonatal management options.

Precis: CTLN1 carrier rates vary amongst different ethnic groups

Keywords: Citrullinemia type 1; Carrier rate; Ethnic groups