Background
Methods
The clinic
The patients
Array-CGH analysis
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pathogenic: anomalies mapping on genomic regions associated to known syndromes or involving known dosage-sensitive genes and large imbalances of de novo origin or inherited from a similarly affected parent;
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likely pathogenic: small alterations of de novo origin or inherited from a parent with a similar phenotype, involving genomic regions or genes whose possible association with clinical conditions has not been definitely identified, but could be supposed from the clinical databases (DECIPHER, ISCA and Troina);
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benign: polymorphic variants reported in several healthy individuals in more than one study within DGV and/or alterations detected in at least two patients with clearly distinct phenotypes of the present cohort;
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likely benign: microdeletions and microduplications reported in few controls in DGV, but defined benign or likely benign in the clinical databases (DECIPHER, ISCA and Troina) and inherited from a normal parent;
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of unknown significance: inherited alterations not described or with discordant definitions among those databases [12].
Statistical analysis
Results
Patient No. | Karyotype |
---|---|
5 | 47,XX,del(6)(q24),+mar[30]/46,XX,del(6)(q24)[15] |
12 | 45,XY,t(5;15)(p15.3;q11.2) |
25 | 46,XY,dup(19)(q12q13.2) |
6 | 46,XY,der(9)t(1;9)(q41;q34) |
26 | 46,XY,r(22).ish del(22q13) |
Variable | Patients with pathogenic CNVs | Patients with benign CNVs | Patients with unknown CNVs |
---|---|---|---|
N = 27 | N = 12 | N = 2 | |
Type
| |||
Deletion | 21 (77.8%) | 2 (16.7%) | |
Duplication | 3 (11.1%) | 9 (75.0%) | 2 (100%) |
Duplication and deletion | 3 (11.1%) | 1 (8.3%) | |
No. CNVs
| |||
1 | 22 | 8 | 2 |
≥2 | 5 | 4 | |
Size
| |||
≤0.5 Mb | 6 (50%) | 2 (100%) | |
>0.5 Mb | 27 (100%) | 6 (50%) | |
Inheritance
| |||
De novo | 21 (77.8%) | 1 (8.3%) | |
Familial | 5 (18.5%) | 7 (58.3%) | 2 (100%) |
Unknown | 1 (3.7%) | 4 (33.3) |
Patient No. | Sex | Type | Locus | Genomic coordinates | Inheritance | Syndrome | OMIM |
---|---|---|---|---|---|---|---|
1 | M | del | 1p36.33p36.31 | chr1:837,491-6,458,739 | de novo | 1p36.33 deletion S. | 607872 |
2 | F | del | 1p36.33p36.31 | chr1:544,268-5,983,997 | de novo | 1p36.33 deletion S. | 607872 |
3 | F | del | 1p36.22p36.13 | chr1:11,722,823-17,104,536 | de novo | - | |
del | 1p35.1p34.1 | chr1:31,080,722-32,355,071 | de novo | - | |||
4 | F | del | 1q23.3q24.2 | chr:162,345,741-169,317,061 | de novo | - | |
5 | F | del | 1q41 | chr1:217,316,641-218,402,514 | not known | 1q41-1q42 deletionS. | 612530 |
del | 6q24.2 | chr6:144,223,274-144,446,997 | not known | - | |||
6 Ref [14] | M | dup | 1q42qter | chr1:223,858,274-248,105,710 | de novo | - | |
7 | F | del | 2q14.3 | chr2:125,049,268-129,322,082 | de novo | - | |
8 | F | del | 2q24.3 | chr2:166,198,780-166,930,047 | de novo | - | |
9 | M | dup | 4p15.32 | chr4:26,509-27,414 | de novo | - | |
del | 17q24.2 | chr17:64,682,538-65,991,538 | de novo | - | |||
10 | M | del | 4q26q28.1 | chr4:117,685,833-127,471,713 | de novo | - | |
11 | M | dup | 4q33q35.1 | chr4:171,936,073-186,883,667 | de novo | - | |
del | 4q35.1q35.2 | chr4:186,913,016-190,976,417 | de novo | - | |||
12 Ref [15] | M | del | 5p15.33p15.32 | chr5:22,178-5,539,182 | paternal | Cri du Chat S. | 123450 |
13 | F | del | 5q14.3q15 | chr5:89,535,781-92,554,566 | de novo | - | |
14 | M | del | 5q23.2q31.1 | chr5:124,391,181-134,632,894 | de novo | - | |
15 | F | del | 6q27 | chr6:168,378,740-169,862,121 | de novo | - | |
16 | M | del | 7q11.23 | chr7:72,039,051-73,771,238 | de novo | Williams-Beuren S. | 194050 |
17 | M | del | 7q21.13q21.3 | chi7:89,993,838-96,278,971 | de novo | Split Hand Foot Malformation 1 with sensorineural hearing loss | 220600 |
18 | M | del | 7q31.1q31.2 | chr7:113,824,764-115,669,764 | de novo | - | |
19 | F | del | 7q36 | chr7:153,669,067-159,107,239 | de novo | Holoprosencephaly-3 | 142945 |
20 | F | del | 15q13.2q13.3 | chr15:31,014,000-32,510,000 | maternal | - | |
21 | F | del | 15q26.3 | chr15:99,836,103-102,351,195 | paternal | 15q26-qter deletion S. | 612626 |
22 | F | dup | 16p13.11p12.3 | chr16:15,492,317-17,804,366 | maternal | - | |
23 | F | del | 17q12 | chr17:31,891,355-33,726,698 | de novo | 17q12 deletion S | 614527 |
24 | M | del | 19p13.3 | chr19:64,447-721,353 | de novo | - | |
25 Ref [16] | M | dup | 19q12q13.2 | chr19:28,272,160-40,699,160 | de novo | - | |
26 | M | del | 22q13.31 | chr22:45,576,757-51,178,264 | de novo | Phelan Mc Dermid S. | 606232 |
dup | Xq28 | chrX:153,322,653-153,406,233 | de novo | - | |||
27 | F | del | 22q11.21 | chr22:19,375,985-21,382,953 | maternal | DiGeorge S. | 188400 |
Clinical variables | Odds ratio | Std. Err. | P | [95% conf. interval] |
---|---|---|---|---|
Early onset of symptoms (before 1 yr of age) | 2.567 | 1.331 | 0.069 | 0.930 - 7.090 |
Dysmorphisms | 3.326 | 1.752 | 0.023 | 1.184 - 9.340 |
Malformations | 5.365 | 2.871 | 0.002 | 1.880 - 15.312 |