Low D4Z4 copy number and gender difference in Korean patients with facioscapulohumeral muscular dystrophy type 1

• We analyzed clinical and genetic spectra of 104 Korean FSHD patients.
• Median D4Z4 copy number was 4 units and 95% Korean FSHD patients carried 1–6 units.
• Disease severity was significantly correlated with D4Z4 copy number.
• Women were more severely affected than men in Korean FSHD patients.

The objective of this study was to investigate the clinical and genetic features of Korean patients with facioscapulohumeral muscular dystrophy type 1 (FSHD), and assessed the impact of molecular defects on phenotypic expression. We enrolled 104 FSHD patients from 87 unrelated Korean families with D4Z4 repeat array of less than 11 copies on 4q35. Sixty-one men and forty-three women were enrolled. Median D4Z4 copy number was 4 units and 99 (95%) Korean patients with FSHD carried 1–6 units. The median age at symptom onset was 13 [interquartile range: 8–17] years old. In 100 symptomatic patients, muscle weakness began in facial muscles in 58 patients, shoulder-girdle muscles in 37, and pelvic-girdle muscles in 5. Disease severity was significantly correlated with D4Z4 copy number. In addition, women were more severely affected than men even though there were no differences in age at examination or in D4Z4 copy number between the two genders. This gender difference among Korean patients was the opposite of analysis on individuals of European ancestry. In conclusion, the present study demonstrated the new diagnostic threshold for FSHD in Koreans based on the D4Z4 repeat array size distribution from 1 to 6 units and expanded the clinical spectrum.