Characterization of FMR1 CGG Repeat Structure and AGG Interruption Patterns in Turkish and Syrian Individuals: CGG Repeats and AGG Interruptions in FMR1

Authors

Hatice Koçak Eker Clinic of Medical Genetics, Konya City Hospital, Konya, Türkiye
Sümeyye Kara Clinic of Medical Genetics, Konya City Hospital, Konya, Türkiye
Fahrettin Duymuş Clinic of Medical Genetics, Konya City Hospital, Konya, Türkiye; Department of Medical Genetics, Uşak University, Faculty of Medicine, Uşak, Türkiye
Büşra Eser Çavdartepe Clinic of Medical Genetics, Konya City Hospital, Konya, Türkiye
Ebru Tuncez Clinic of Medical Genetics, Konya City Hospital, Konya, Türkiye
Özgür Balasar Clinic of Medical Genetics, Konya City Hospital, Konya, Türkiye
Müşerref Başdemirci Clinic of Medical Genetics, Konya City Hospital, Konya, Türkiye
Tuğba Akın Duman Clinic of Medical Genetics, Konya City Hospital, Konya, Türkiye
Levent Şimşek Clinic of Medical Genetics, Konya City Hospital, Konya, Türkiye

Keywords:

AGG interruption, FMR1 gene, genetic variation, population genetics, trinucleotide repeat expansion, uninterrupted CGG tract

Abstract

Objective: This study aimed to characterize FMR1 CGG repeat length, AGG interruption number and patterns, and uninterrupted CGG tract architecture in Turkish and Syrian individuals referred for FMR1-associated phenotypes and evaluate their implications for repeat instability.
Methods: This retrospective study analysed 513 alleles from 351 unrelated individuals (162 females, 189 males), including 476 Turkish and 37 Syrian alleles. CGG repeat length, AGG interruption count and interspersion patterns, and the length and positional distribution of uninterrupted CGG tracts were assessed. Allele classifications and family transmission data were evaluated when available.
Results: Alleles with two AGG interruptions were the most prevalent configuration in both cohorts (70% in Turkish and 58% in Syrian alleles). In the Turkish cohort, 117 patterns were observed, including 56 population-specific variants; in the Syrian cohort, 23 distinct patterns were detected, of which seven were unique. The most common CGG repeat size was 30 in both cohorts. The most frequent AGG interspersion patterns were (CGG)9-AGG-(CGG)9-AGG-(CGG)10 and (CGG)9-AGG-(CGG)9-AGG-(CGG)9. Among 53 normal alleles with uninterrupted CGG tracts of >20 repeats, 94.3% were located at the 5′ end and were significantly associated with a positive family history (p = 0.004). All alleles that expanded to full mutations lacked AGG interruptions.
CONCLUSION: These findings demonstrate marked variability in FMR1 CGG repeat length and AGG interruption architecture in Turkish and Syrian populations, although the small sample size of the Syrian cohort warrants cautious interpretation. The data further suggest that repeat instability is associated not only with repeat number but also with repeat structure and positional context. Incorporating AGG interruption analysis into routine FMR1 testing may improve genetic counseling and risk stratification.