Genetic defects of CHM and visual acuity outcome in 24 choroideremia patients from 16 Japanese families

Abstract

Choroideremia (CHM) is an incurable progressive chorioretinal dystrophy. Little is known about the natural disease course of visual acuity in the Japanese population. We aimed to investigate the genetic spectrum of the CHM gene and visual acuity outcomes in 24 CHM patients from 16 Japanese families. We measured decimal best-corrected visual acuity (BCVA) at presentation and follow-up, converted to logMAR units for statistical analysis. Sanger and/or whole-exome sequencing were performed to identify pathogenic CHM variants/deletions. The median age at presentation was 37.0 years (range, 5–76 years). The mean follow-up interval was 8.2 years. BCVA of the better-seeing eye at presentation was significantly worsened with increasing age (r = 0.515, p < 0.01), with a high rate of BCVA decline in patients > 40 years old. A Kaplan–Meier survival curve suggested that a BCVA of Snellen equivalent 20/40 at follow-up remains until the fifties. Fourteen pathogenic variants, 6 of which were novel [c.49 + 5G > A, c.116 + 5G > A, p.(Gly176Glu, Glu177Ter), p.Tyr531Ter, an exon 2 deletion, and a 5.0-Mb deletion], were identified in 15 families. No variant was found in one family only. Our BCVA outcome data are useful for predicting visual prognosis and determining the timing of intervention in Japanese patients with CHM variants.

Clinical and genetic findings in a Chinese cohort with choroideremia

“…Considering the small numbers of Chinese patients in our cohort, we combined our patients with the 68 Chinese patients described in six previous studies [13][14][15][16][17][18] and calculated a transition age using the method of function fitting combined with preset piecewise regression. Our results showed a transition age of 25 years, which was relatively close to the age of 30 years described by Heon et al [25], but much younger than the ages described in several Caucasian studies [9,10,12,24] and a transition age of 40 years recently reported in Japanese patients [26]. The estimated rate for the decline in BCVA after the age of 25 years was 0.037logMAR/year, which was between 0.025-0.048 logMAR/year [10][11][12]27].…”

Genotype-Phenotype Correlations in RP1-Associated Retinal Dystrophies: A Multi-Center Cohort Study in JAPAN

“…We studied a total of 607 patients with inherited retinal diseases (IRDs) from 440 families, including 475 patients from 344 families at The Jikei University Hospital, 100 patients from 67 families at Nippon Medical School Chiba Hokusoh Hospital, 23 patients from 22 families at University of Occupational and Environmental Health Hospital, and 9 patients from 7 families at Hamamatsu University Hospital, who underwent whole-exome sequencing (WES) or whole-genome sequencing (WGS) analysis. Details of the WES and WGS methodologies have been described previously [ 26 , 27 , 28 , 29 , 30 , 31 ]. We evaluated the pathogenicity of the obtained RP1 variants according to the frequency using the Human Gene Mutation Database Professional (HGMD, , accessed on January, 2020), Genome Aggregation Database (gnomAD, , accessed on 29 October 2020), inheritance pattern, phenotype, and American College of Medical Genetics standards (ACMG) criteria.…”