Table 2.
Number and diagnostic yield (in parentheses) of pediatric and prenatal cases by genetic ancestry bins, stratified by mode of inheritance, and Cochran-Armitage (C-A) test Z-statistics for trend tests of positive versus negative and inconclusive versus negative cases.
| Number of Cases & (%) in Each Bin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ancestry | Case definition | Mode of inheritance | N | 0–12.5% | 12.5–37.5% | 37.5–62.5% | 62.5–87.5% | 87.5–100% | C-A test Z-statistic |
| Pediatric cases | |||||||||
| African | Positive | Autosomal dominant | 99 |
87 (0.18) |
5 (0.25) |
2 (0.2) |
4 (0.22) |
1 (0.17) |
0.23 |
| Autosomal recessive | 25 |
22 (0.05) |
2 (0.1) |
1 (0.1) |
0 (0) |
0 (0) |
−0.46 | ||
| X-linked | 17 | 17 (0.04) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−1.23 | ||
| All | 141 |
126 (0.27) |
7 (0.35) |
3 (0.3) |
4 (0.22) |
1 (0.17) |
−0.34 | ||
| Inconclusive | Autosomal dominant | 30 |
25 (0.05) |
3 (0.15) |
2 (0.2) |
0 (0) |
0 (0) |
0.01 | |
| Autosomal recessive | 32 |
30 (0.06) |
0 (0) |
0 (0) |
1 (0.06) |
1 (0.17) |
−0.09 | ||
| X-linked | 11 |
10 (0.02) |
0 (0) |
1 (0.1) |
0 (0) |
0 (0) |
−0.21 | ||
| All | 73 |
65 (0.14) |
3 (0.15) |
3 (0.3) |
1 (0.06) |
1 (0.17) |
−0.13 | ||
| Negative | Negative | 315 |
284 (0.6) |
10 (0.5) |
4 (0.4) |
13 (0.72) |
4 (0.67) |
||
| Total | 529 | 475 | 20 | 10 | 18 | 6 | |||
| Native American | Positive | Autosomal dominant | 99 |
42 0.18) |
15 (0.22) |
29 (0.19) |
8 (0.15) |
5 (0.23) |
−0.17 |
| Autosomal recessive | 25 |
15 (0.06) |
2 (0.03) |
7 (0.05) |
0 (0) |
1 (0.05) |
−1.59 | ||
| X-linked | 17 |
7 (0.03) |
1 (0.01) |
8 (0.05) |
1 (0.02) |
0 (0) |
−0.10 | ||
| All | 141 |
64 (0.27) |
18 (0.27) |
44 (0.29) |
9 (0.17) |
6 (0.27) |
−0.75 | ||
| Inconclusive | Autosomal dominant | 30 |
16 (0.07) |
4 (0.06) |
6 (0.04) |
4 (0.08) |
0 (0) |
−1.16 | |
| Autosomal recessive | 32 |
16 (0.07) |
2 (0.03) |
10 (0.07) |
2 (0.04) |
2 (0.09) |
−0.35 | ||
| X-linked | 11 |
5 (0.02) |
0 (0) |
5 (0.03) |
1 (0.02) |
0 (0) |
−0.06 | ||
| All | 73 |
37 (0.16) |
6 (0.09) |
21 (0.14) |
7 (0.13) |
2 (0.09) |
−0.95 | ||
| Negative | Negative | 315 |
136 (0.57) |
43 (0.64) |
85 (0.57) |
37 (0.7) |
14 (0.64) |
||
| Total | 529 | 237 | 67 | 150 | 53 | 22 | |||
| East Asian | Positive | Autosomal dominant | 99 |
89 (0.19) |
3 (0.23) |
6 (0.55) |
0 (0) |
1 (0.04) |
−0.97 |
| Autosomal recessive | 25 |
22 (0.05) |
1 (0.08) |
0 (0) |
0 (0) |
2 (0.08) |
0.34 | ||
| X-linked | 17 |
14 (0.03) |
1 (0.08) |
0 (0) |
0 (0) |
2 (0.08) |
0.97 | ||
| All | 141 |
125 (0.26) |
5 (0.38) |
6 (0.55) |
0 (0) |
5 (0.21) |
−0.32 | ||
| Inconclusive | Autosomal dominant | 30 |
28 (0.06) |
0 (0) |
1 (0.09) |
0 (0) |
1 (0.04) |
−0.51 | |
| Autosomal recessive | 32 |
30 (0.06) |
0 (0) |
0 (0) |
0 (0) |
2 (0.08) |
−0.24 | ||
| X-linked | 11 |
11 (0.02) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−1.01 | ||
| All | 73 |
69 (0.14) |
0 (0) |
1 (0.09) |
0 (0) |
3 (0.13) |
−0.83 | ||
| Negative | Negative | 315 |
283 (0.59) |
8 (0.62) |
4 (0.36) |
4 (1) |
16 (0.67) |
||
| Total | 529 | 477 | 13 | 11 | 4 | 24 | |||
| European | Positive | Autosomal dominant | 99 |
11 (0.11) |
39 (0.2) |
24 (0.24) |
8 (0.17) |
17 (0.2) |
0.86 |
| Autosomal recessive | 25 |
7 (0.07) |
10 (0.05) |
3 (0.03) |
0 (0) |
5 (0.06) |
−0.87 | ||
| X-linked | 17 |
2 (0.02) |
9 (0.05) |
0 (0) |
2 (0.04) |
4 (0.05) |
0.44 | ||
| All | 141 |
20 (0.21) |
58 (0.29) |
27 (0.27) |
10 (0.22) |
26 (0.3) |
0.49 | ||
| Inconclusive | Autosomal dominant | 30 |
5 (0.05) |
9 (0.05) |
6 (0.06) |
5 (0.11) |
5 (0.06) |
0.74 | |
| Autosomal recessive | 32 |
12 (0.12) |
15 (0.08) |
1 (0.01) |
2 (0.04) |
2 (0.02) |
−2.91 | ||
| X-linked | 11 |
2 (0.02) |
3 (0.02) |
2 (0.02) |
1 (0.02) |
3 (0.03) |
0.79 | ||
| All | 73 |
19 (0.2) |
27 (0.14) |
9 (0.09) |
8 (0.17) |
10 (0.11) |
−1.08 | ||
| Negative | Negative | 315 |
58 (0.6) |
115 (0.58) |
63 (0.64) |
28 (0.61) |
51 (0.59) |
||
| Total | 529 | 97 | 200 | 99 | 46 | 87 | |||
| Middle Eastern | Positive | Autosomal dominant | 99 |
77 (0.19) |
22 (0.19) |
0 (0) |
0 (0) |
0 (0) |
−0.55 |
| Autosomal recessive | 25 |
19 (0.05) |
5 (0.04) |
0 (0) |
0 (0) |
1 (0.11) |
0.92 | ||
| X-linked | 17 |
12 (0.03) |
5 (0.04) |
0 (0) |
0 (0) |
0 (0) |
0.31 | ||
| All | 141 |
108 (0.27) |
32 (0.28) |
0 (0) |
0 (0) |
1 (0.11) |
0.03 | ||
| Inconclusive | Autosomal dominant | 30 |
21 (0.05) |
5 (0.04) |
1 (0.5) |
1 (0.33) |
2 (0.22) |
2.97 | |
| Autosomal recessive | 32 |
20 (0.05) |
8 (0.07) |
0 (0) |
0 (0) |
4 (0.44) |
4.11* | ||
| X-linked | 11 |
8 (0.02) |
2 (0.02) |
0 (0) |
0 (0) |
1 (0.11) |
1.70 | ||
| All | 73 |
49 (0.12) |
15 (0.13) |
1 (0.5) |
1 (0.33) |
7 (0.78) |
4.29* | ||
| Negative | Negative | 315 |
243 (0.61) |
68 (0.59) |
1 (0.5) |
2 (0.67) |
1 (0.11) |
||
| Total | 529 | 400 | 115 | 2 | 3 | 9 | |||
| South Asian | Positive | Autosomal dominant | 99 |
92 (0.19) |
1 (0.5) |
0 (0) |
3 (0.19) |
3 (0.23) |
0.43 |
| Autosomal recessive | 25 |
20 (0.04) |
0 (0) |
2 (0.4) |
1 (0.06) |
2 (0.15) |
2.47 | ||
| X-linked | 17 |
17 (0.03) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−1.00 | ||
| All | 141 |
129 (0.26) |
1 (0.5) |
2 (0.4) |
4 (0.25) |
5 (0.38) |
0.96 | ||
| Inconclusive | Autosomal dominant | 30 |
30 (0.06) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−1.33 | |
| Autosomal recessive | 32 |
27 (0.05) |
0 (0) |
0 (0) |
3 (0.19) |
2 (0.15) |
2.28 | ||
| X-linked | 11 |
11 (0.02) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−0.81 | ||
| All | 73 |
68 (0.14) |
0 (0) |
0 (0) |
3 (0.19) |
2 (0.15) |
0.48 | ||
| Negative | Negative | 315 |
296 (0.6) |
1 (0.5) |
3 (0.6) |
9 (0.56) |
6 (0.46) |
||
| Total | 529 | 493 | 2 | 5 | 16 | 13 | |||
| Prenatal cases | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| African | Positive | Autosomal dominant | 39 |
38 (0.13) |
1 (0.07) |
0 (0) |
0 (0) |
0 (0) |
−1.46 |
| Autosomal recessive | 15 |
15 (0.05) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−1.05 | ||
| X-linked | 6 |
6 (0.02) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−0.67 | ||
| All | 60 |
59 (0.2) |
1 (0.07) |
0 (0) |
0 (0) |
0 (0) |
−1.90 | ||
| Inconclusive | Autosomal dominant | 11 |
7 (0.02) |
4 (0.29) |
0 (0) |
0 (0) |
0 (0) |
0.86 | |
| Autosomal recessive | 6 |
6 (0.02) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−0.67 | ||
| X-linked | 2 |
2 (0.01) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−0.39 | ||
| All | 19 |
15 (0.05) |
4 (0.29) |
0 (0) |
0 (0) |
0 (0) |
0.16 | ||
| Negative | Negative | 237 |
216 (0.74) |
9 (0.64) |
4 (1) |
5 (1) |
3 (1) |
||
| Total | 316 | 290 | 14 | 4 | 5 | 3 | |||
| Native American | Positive | Autosomal dominant | 39 |
27 (0.11) |
6 (0.17) |
5 (0.16) |
1 (0.1) |
0 (0) |
0.56 |
| Autosomal recessive | 15 |
12 (0.05) |
1 (0.03) |
2 (0.06) |
0 (0) |
0 (0) |
−0.36 | ||
| X-linked | 6 |
5 (0.02) |
0 (0) |
0 (0) |
1 (0.1) |
0 (0) |
0.27 | ||
| All | 60 |
44 (0.18) |
7 (0.19) |
7 (0.23) |
2 (0.2) |
0 (0) |
0.35 | ||
| Inconclusive | Autosomal dominant | 11 |
8 (0.03) |
1 (0.03) |
2 (0.06) |
0 (0) |
0 (0) |
0.18 | |
| Autosomal recessive | 6 |
5 (0.02) |
0 (0) |
0 (0) |
1 (0.1) |
0 (0) |
0.27 | ||
| X-linked | 2 |
2 (0.01) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−0.71 | ||
| All | 19 |
15 (0.06) |
1 (0.03) |
2 (0.06) |
1 (0.1) |
0 (0) |
0.06 | ||
| Negative | Negative | 237 |
179 (0.75) |
28 (0.78) |
22 (0.71) |
7 (0.7) |
1 (1) |
||
| Total | 316 | 238 | 36 | 31 | 10 | 1 | |||
| East Asian | Positive | Autosomal dominant | 39 |
32 (0.12) |
1 (0.2) |
3 (0.19) |
0 (0) |
3 (0.11) |
0.13 |
| Autosomal recessive | 15 |
13 (0.05) |
0 (0) |
0 (0) |
0 (0) |
2 (0.07) |
0.23 | ||
| X-linked | 6 |
5 (0.02) |
0 (0) |
1 (0.06) |
0 (0) |
0 (0) |
−0.26 | ||
| All | 60 |
50 (0.19) |
1 (0.2) |
4 (0.25) |
0 (0) |
5 (0.18) |
0.14 | ||
| Inconclusive | Autosomal dominant | 11 |
7 (0.03) |
1 (0.2) |
1 (0.06) |
1 (0.33) |
1 (0.04) |
1.22 | |
| Autosomal recessive | 6 |
5 (0.02) |
0 (0) |
1 (0.06) |
0 (0) |
0 (0) |
−0.26 | ||
| X-linked | 2 |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
2 (0.07) |
4.09* | ||
| All | 19 |
12 (0.05) |
1 (0.2) |
2 (0.13) |
1 (0.33) |
3 (0.11) |
2.04 | ||
| Negative | Negative | 237 |
202 (0.77) |
3 (0.6) |
10 (0.63) |
2 (0.67) |
20 (0.71) |
||
| Total | 316 | 264 | 5 | 16 | 3 | 28 | |||
| European | Positive | Autosomal dominant | 39 |
6 (0.1) |
5 (0.1) |
6 (0.14) |
8 (0.12) |
14 (0.15) |
0.75 |
| Autosomal recessive | 15 |
5 (0.09) |
2 (0.04) |
0 0) |
3 (0.04) |
5 (0.05) |
−0.58 | ||
| X-linked | 6 |
1 (0.02) |
0 (0) |
1 (0.02) |
1 (0.01) |
3 (0.03) |
0.88 | ||
| All | 60 |
12 (0.21) |
7 (0.13) |
7 (0.16) |
12 (0.18) |
22 (0.23) |
0.56 | ||
| Inconclusive | Autosomal dominant | 11 |
2 (0.03) |
3 (0.06) |
3 (0.07) |
2 (0.03) |
1 (0.01) |
−1.26 | |
| Autosomal recessive | 6 |
1 (0.02) |
2 (0.04) |
1 (0.02) |
0 (0) |
2 (0.02) |
−0.48 | ||
| X-linked | 2 |
2 (0.03) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−2.18 | ||
| All | 19 |
5 (0.09) |
5 (0.1) |
4 (0.09) |
2 (0.03) |
3 (0.03) |
−1.89 | ||
| Negative | Negative | 237 |
41 (0.71) |
40 (0.77) |
33 (0.75) |
54 (0.79) |
69 (0.73) |
||
| Total | 316 | 58 | 52 | 44 | 68 | 94 | |||
| Middle Eastern | Positive | Autosomal dominant | 39 |
29 (0.12) |
9 (0.15) |
1 (0.2) |
0 (0) |
0 (0) |
0.12 |
| Autosomal recessive | 15 |
11 (0.04) |
3 (0.05) |
0 (0) |
0 (0) |
1 (0.25) |
1.20 | ||
| X-linked | 6 |
5 (0.02) |
1 (0.02) |
0 (0) |
0 (0) |
0 (0) |
−0.44 | ||
| All | 60 |
45 (0.18) |
13 (0.21) |
1 (0.2) |
0 (0) |
1 (0.25) |
0.54 | ||
| Inconclusive | Autosomal dominant | 11 |
10 (0.04) |
1 (0.02) |
0 (0) |
0 (0) |
0 (0) |
−1.02 | |
| Autosomal recessive | 6 |
5 (0.02) |
0 (0) |
0 (0) |
0 (0) |
1 (0.25) |
1.55 | ||
| X-linked | 2 |
2 (0.01) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−0.66 | ||
| All | 19 |
17 (0.07) |
1 (0.02) |
0 (0) |
0 (0) |
1 (0.25) |
−0.05 | ||
| Negative | Negative | 237 |
183 (0.75) |
48 (0.77) |
4 (0.8) |
0 (0) |
2 (0.5) |
||
| Total | 316 | 245 | 62 | 5 |
0 (0) |
4 | |||
| South Asian | Positive | Autosomal dominant | 39 |
36 (0.12) |
0 (0) |
2 (0.4) |
0 (0) |
1 (0.06) |
−0.32 |
| Autosomal recessive | 15 |
13 (0.04) |
0 (0) |
0 (0) |
0 (0) |
2 (0.11) |
1.05 | ||
| X-linked | 6 |
6 (0.02) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−0.66 | ||
| All | 60 |
55 (0.19) |
0 (0) |
2 (0.4) |
0 (0) |
3 (0.17) |
0.07 | ||
| Inconclusive | Autosomal dominant | 11 |
10 (0.03) |
0 (0) |
0 (0) |
0 (0) |
1 (0.06) |
0.36 | |
| Autosomal recessive | 6 |
5 (0.02) |
0 (0) |
1 (0.2) |
0 (0) |
0 (0) |
0.19 | ||
| X-linked | 2 |
2 (0.01) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
−0.38 | ||
| All | 19 |
17 (0.06) |
0 (0) |
1 (0.2) |
0 (0) |
1 (0.06) |
0.26 | ||
| Negative | Negative | 237 |
220 (0.75) |
1 (1) |
2 (0.4) |
0 (0) |
14 (0.78) |
||
| Total | 316 | 292 | 1 | 5 |
0 (0) |
18 | |||
*Indicates a C-A test Z-statistic with P value < 0.0007.
Note: Values in bold indicate the combined Autosomal dominant, Autosomal recessive, and X-linked cases.