Rare diseases in the Turkish-Cypriot community: a nationwide study

Minor or genetically isolated populations like Turkish-Cypriots (TC) are usually challenging to diagnose and treat for uncommon genetic diseases. TC may exhibit several patterns of unusual genetic disorders based on their unique historical and demographic conditions. The objective of the current study is to identify and investigate the rarest genetic disorders in TC patients. Therefore, between 2019 and 2025, clinical and genetic data, which were confirmed by gene panels and exome sequencing, from 150 TC patients were retrospectively analysed in our clinic. Also, inheritance models and variant types were classified and contrasted. Out of 150 patients, 123 different rare diseases were discovered. Observed in 10 cases (6.7%), neurofibromatosis (type 1) was the most common of these, trailed by spinal muscular atrophy in 6 cases (4%), phenylketonuria in 6 cases (4%), and episodic kinesigenic dyskinesia type 1 in 4 cases (2.7%). Importantly, 114 of the discovered diseases (76%) were observed in only one patient, indicating a vast spectrum of ultrarare or single-case conditions within the group. Autosomal dominant was the most prevalent mode of inheritance; other types also present were autosomal recessive and mitochondrial inheritance. The recurrence of particular gene pathogenic variants in a group of patients may suggest a potential founder effect; however, further population-based haplotype studies are required to confirm this hypothesis within the TC population. The results demonstrate an overrepresentation of particular neurogenetic syndromes and underline the necessity of targeted screening procedures and population-dependent databases to maximise diagnostic yield and genetic counselling in this poorly characterised population.