Evaluation of carrier frequencies of phenylketonuria, congenital hypothyroidism, biotinidase deficiency, and cystic fibrosis included in the national newborn screening program in Türkiye using next-generation sequencing

This study aims to evaluate the carrier frequencies and genetic variant diversity of four inherited diseases included in Turkey's national newborn screening program: phenylketonuria (PKU), congenital hypothyroidism (CH), biotinidase deficiency (BD), and cystic fibrosis (CF). A total of 1966 individuals, who presented with indications other than these diseases and reported no parental consanguinity, were included in the study. Clinical exome sequencing data obtained via next-generation sequencing (NGS) technology were retrospectively analyzed. As a result, carrier frequencies were identified as 7.07% for PKU, 8.24% for CH, 8.49% for BD, and 6.25% for CF, yielding a total carrier rate of 27.26%. Based on these frequencies, estimated incidence rates were calculated using the Hardy–Weinberg equilibrium equation and assessed in conjunction with epidemiological data reported in the literature. For each disease, the most common variants were identified and compared with both national and international literature. The findings provide important insights into the genetic carrier profile of the Turkish population and offer a scientific basis for improving preventive healthcare services such as preconception screening, partner screening, and prenatal diagnosis. The results also support the view that the incidence and carrier frequencies of these diseases in Turkey are higher than global averages. This study highlights the need to reinforce current newborn screening strategies with genetic data and serves as a guiding resource for the development of future genome-based public health policies.