Table 2.
Clinical features and repeat expansion detection in patients from the 100 000 Genomes Project
|
All patients tested |
Patients with confirmed repeat expansions |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sex |
|||||||||||||
| Number of patients, n (families, n) | Age, years, median (range) | Male | Female | Mean age at onset, years + months (SD) | Family history, n (%) | Repeat expansion called | Repeat expansion after visual inspection | Repeat expansion tested by PCR | Repeat expansion confirmed, n (families, n) | Mean age at onset, years + months (SD) | Family history, n (%) | ||
| Overall | 11 631 (10 417) | 16 (9–39) | 6677 (57%) | 4954 (43%) | 12+5 (20+3) | 3139 (27%) | 293 | 105 | 81 | 68 (60) | 26+4 (23+9) | 29 (48%) | |
| Panel A (AR, ATN1, ATXN1, ATXN2, ATXN3, ATXN7, C9ORF72, CACNA1A, FMR1, FXN, HTT, and TBP) | |||||||||||||
| Hereditary ataxia | 1182 (1049) | 55 (36–68) | 597 (51%) | 585 (49%) | 35+6 (22+6) | 403 (34%) | 51 | 22 | 19 | 19 (18) | 39+3 (16+0) | 9 (50%) | |
| Hereditary spastic paraplegia | 526 (448) | 44 (29–60) | 275 (52%) | 251 (48%) | 25+10 (20+0) | 221 (42%) | 15 | 8 | 4 | 3 (3) | 21+0 (0)* | 0 | |
| Early-onset and familial Parkinson's disease | 520 (508) | 57 (50–67) | 304 (58%) | 216 (42%) | 44+0 (13+3) | 5 (1%) | 16 | 4 | 2 | 2 (2) | 36+0 (16+3) | 1 (50%) | |
| Complex parkinsonism | 150 (148) | 65 (55–72) | 85 (57%) | 65 (43%) | 48+5 (18+10) | 31 (21%) | 10 | 3 | 2 | 2 (2) | 44+6 (0+8) | 1 (50%) | |
| Early-onset dystonia | 298 (268) | 34 (20–52) | 116 (39%) | 182 (61%) | 22+0 (16+3) | 104 (35%) | 9 | 2 | 0 | 0 | .. | 0 | |
| Early-onset dementia | 151 (145) | 63 (58–71) | 74 (49%) | 77 (51%) | 53+11 (13+0) | 88 (58%) | 17 | 7 | 5 | 4 (4) | 48+4 (12+6) | 2 (50%) | |
| Amyotrophic lateral sclerosis | 107 (105) | 51 (41–67) | 69 (64%) | 38 (36%) | 42+6 (16+4) | 19 (18%) | 9 | 8 | 8 | 8 (7) | 51+2 (15+11) | 6 (86%) | |
| Charcot-Marie-Tooth disease | 692 (587) | 54 (33–69) | 410 (59%) | 282 (41%) | 31+0 (22+0) | 278 (40%) | 18 | 7 | 4 | 4 (4) | 20+3 (25+9) | 1 (25%) | |
| Ultra-rare undescribed monogenic disorders | 62 (55) | 44 (28–62) | 21 (34%) | 41 (66%) | 17+9 (20+1) | 19 (31%) | 5 | 3 | 3 | 3 (2) | 31+0 (26+10) | 2 (100%) | |
| Overall panel A | 3692 (3305) | 55 (41–68) | 1954 (53%) | 1738 (47%) | 34+10 (21+5) | 1336 (36%) | 150 | 64 | 47 | 45 (42) | 38+6 (19+3) | 22 (52%) | |
| Panel B (ATN1, ATXN1, ATXN2, ATXN3, ATXN7, CACNA1A, and HTT) | |||||||||||||
| Complex intellectual disability† | 2743 (2492) | 12 (8–19) | 1522 (55%) | 1221 (45%) | 1+7 (5+3) | 528 (19%) | 14 | 9 | 8 | 8 (8) | 0+6 (1+0) | 1 (13%) | |
| Panel C (DMPK) | |||||||||||||
| Congenital myopathy | 471 (422) | 21 (13–44) | 259 (55%) | 212 (45%) | 11+1 (18+0) | 116 (25%) | 1 | 1 | 1 | 1 (1) | 30+0 (0) | 1 (100%) | |
| Distal myopathies | 185 (167) | 58 (42–68) | 120 (65%) | 65 (35%) | 36+11 (22+3) | 52 (28%) | 2 | 2 | 2 | 2 (1) | 2+0 (0) | 1 (100%) | |
| Congenital muscular dystrophy | 115 (109) | 25 (13–47) | 58 (50%) | 57 (50%) | 16+0 (19+9) | 24 (21%) | 2 | 2 | 2 | 2 (1) | 0+0 (0) | 1 (100%) | |
| Skeletal muscle channelopathy | 90 (77) | 38 (21–52) | 47 (52%) | 43 (48%) | 16+8 (4+7) | 29 (32%) | 0 | 0 | 0 | 0 | .. | 0 | |
| Overall panel C | 860 (772) | 34 (16–57) | 483 (56%) | 377 (44%) | 17+9 (21+1) | 220 (26%) | 5 | 5 | 5 | 5 (3) | 6+10 (13+0) | 3 (100%) | |
| Panel D (FMR1) | |||||||||||||
| Intellectual disability | 6731 (5998) | 11 (9–15) | 4051 (60%) | 2680 (40%) | 1+1 (3+1) | 1536 (23%) | 124 | 27 | 21 | 10 (10) | 0+1 (0+4) | 1 (10%) | |
Some patients might have been recruited in more than one disease category, and therefore the total number of patients broken down by disease is larger than the total. Ethnicity data are provided in the appendix (p 37). Family history is reported as the absolute number and percentage of patients with positive family history, defined as the presence of at least a first degree or second degree affected relative.
*
Information regarding the age of onset was available for only one individual.
†
Clinical features of patients with complex intellectual disability tested in panel B are provided in the appendix (p 34).