Overview of repeats
In a 2023 study, Cortese et al., 2023 [Preprint]). reported the identification of a CCG repeat expansion in the 5' UTR of the ABCD3 gene, found to be causing Oculopharyngodistal Myopathy (OPDM) in European populations. The pathogenic range for ABCD3 repeats in OPDM, as determined through targeted long-read sequencing of 19 individuals from eight families, was determined to be between 118 and 694 CCG repeats. No repeat expansions at other loci previously implicated in OPDM (LRP12, GIPC1, NOTCH2NLC and RILPL1), nor any other shared candidate repeat expansions among the majority of affected individuals was observed.
Affected males exhibited an average repeat size of 185±23, with a range of 180 repeats. There was a notable negative correlation between the repeat size and age-of-onset in these males, with larger expansions correlating to earlier onset. Conversely, the repeat expansions in affected females were approximately 1.9 times longer, averaging 356±59 repeats and displayed more variability in length (range 576 repeats). Despite the larger expansions, there was no significant correlation between repeat size and age-of-onset in females. Typically, female onset was about 5 years earlier than in males, with an average onset age of 24±2.9 years compared to 29.8±4.9 years in males. The overall average age of onset for the condition was 26.7 years, ranging from 10 to 50 years. Clinically, ptosis was the most common initial symptom in almost all cases (22 out of 24, 92%), with a few presenting with dysphagia or weakness of the oropharyngeal muscles.