Table 4 Clinically relevant findings in a prospective study of 100 cases referred for CMA
Case | Reason for referral | CNVs (ISCN 2016) | Size | Classification | OMIM diagnosis (inheritance pattern) | Added information by WGS |
Fifteen CNVs detected with CMA and WGS | ||||||
 RD_P403 | NDD | arr[GRCh37] 2p21p22.1(39053852_42501893)x3 dn | 3.45 Mb | Likely pathogenic | Not in OMIM | Tandem duplication |
 RD_P404 | NDD | arr[GRCh37] 3p25.2p25.3(9453917_12015126)x3 | 2.56 Mb | Likely Pathogenic | Not in OMIM | Tandem duplication |
 RD_P405 | Growth retardation | arr[GRCh37] 3q25.32q26.1(158567751_160802139)x3 (not paternal) | 2.23 Mb | Likely Pathogenic | Not in OMIM | Duplication inserted on chromosome 13 |
 RD_P406 | NDD, microcephaly | arr[GRCh37] 4q25q35.2(190816609_191024533)x3 dn | 81 Mb | Pathogenic | Not in OMIM | Unbalanced translocation between chr 4 and chr2 |
 RD_P407 | NDD, Arthrogryposis | arr[GRCh37] 7q11.23(72699382_74142329)x1 dn | 1.44 Mb | Pathogenic | #194050 Williams-Beuren syndrome (AD) |  |
 RD_P408 | Short stature, NDD, facial dysmorphism | arr[GRCh37] 7q11.23(72726590_74142329)x1 dn | 1.42 Mb | Pathogenic | #194050 Williams-Beuren syndrome (AD) |  |
 RD_P409 | Hypogonadotropic hypogonadism | arr[GRCh37] 8p11.22(38320755_38328265)x1 dn (exon 1 FGFR1) | 7.52 kb | Pathogenic | #147950 Kallmann syndrome (AD) |  |
 RD_P410 | Duodenal atresia | arr[GRCh37] 9p24.2p24.3(2074076_2381053)x1 pat | 307 kb | VUS | Not in OMIM |  |
 RD_P411 | NDD, Arthrogryposis | arr[GRCh37] 12q13.13(53784698_54741363)x1 dn | 957 kb | Pathogenic | Not in OMIM |  |
 RD_P412 | NDD | arr[GRCh37] 15q13.2q13.3(30405535_32914190)x1 | 2.5 Mb | Pathogenic | #612001 15q13.3 microdeletion syndrome (AD) |  |
 RD_P413 | NDD | arr[GRCh37] 16p11.2(29656717_30158469)x1 | 502 kb | Pathogenic | #611913 16p11.2 microdeletion syndrome (AD) |  |
 RD_P414 | NDD | arr[GRCh37] 18p11.32pter(12774-1652788)x1 dn, 18q22.1qter(62984563_78015117)x1 dn (Ring chromosome) | 1.64 Mb 15 Mb | Pathogenic | Not in OMIM | Detailed structure of derivative chromosome |
 RD_P415 | NDD | arr[GRCh37] 22q11.21(18890264_21540347)x1 | 2.65 Mb | Pathogenic | #188400 DiGeorge syndrome (AD) |  |
 RD_P416 | NDD | arr[GRCh37] 2q23.1(148893848_148944832)x1 (exon 3 MBD5) | 51 kb | VUS | #156200 Intellectual disability 1 (AD) |  |
One CNV detected with WGS | ||||||
 RD_P417 | NDD | arr[GRCh37] 12q24.31(123736705_123740392)x0 (exon 2 C12orf65) | 3.7 kb | Pathogenic | #613559 Combined oxidative phosphorylation deficiency 7 (AR) | Deletion found by WGS and not detected by CMA |
Case | Reason for referral | SNV | Inheritance | Zygosity | OMIM diagnosis | Classification |
Nine SNVs detected with ID in silico gene panel | ||||||
 RD_P418 | NDD, macrocephaly | NSD1, NM_172349, c.5289G>C, p.(Trp1763Cys) | De novo | Heterozygous | #117550 Sotos syndrome (AD) | Likely Pathogenic |
 RD_P419 | NDD (father with similar symptoms) | NKX2-1, NM_003317, c.556delC, p.(Leu186CysfsTer12) | Paternal | Heterozygous | #610978 Choreoathetosis, hypothyroidism and neonatal respiratory distress (AD) | Likely Pathogenic |
 RD_P420 | NDD, white matter abnormality | PNPT1, NM_033109, c.420delG; p.(Leu141SerfsTer17) PNPT1, NM_033109, c.1519G>T, p.(Ala507Ser) | Paternal | Compound heterozygous | #614932 Combined oxidative phosphorylation deficiency 13 (AR) | Likely Pathogenic |
Maternal | ||||||
 RD_P421 | NDD, cleft-lip palate | SATB2, NM_015265, c.652A>T, p.(Lys218Ter) | De novo | Heterozygous | #612313 Glass syndrome (AD) | Pathogenic |
 RD_P422 | Microcephaly, holoprocencephaly | ZIC1, NM_007129, c.1225C>T, p.(Arg409Trp) | De novo | Heterozygous | #616602 Craniosynostosis 6 (AD) | Likely Pathogenic |
 RD_P423 | NDD, macrocephaly | PTEN; NM_000314, c.264T>G; p.(Tyr88Ter) | N.i. | Heterozygous | #158360 Cowden syndrome (AD) | Likely Pathogenic |
 RD_P424 | Respiratory failure, abnormality of corpus callosum | POLG; NM_002693, c.679C>T;679C>T, p.(Arg227Trp) | Paternal/ Maternal | Homozygous | #203700 Mitochondrial DNA depletion syndrome 4A (AR) | Likely Pathogenic |
 RD_P425 | NDD, epilepsy | CLN5, NM_006493, c.595C>T;595C>T, p.(Arg199Ter) | Paternal/ Maternal | Homozygous | #256731 Ceroid lipofuscinosis, neuronal 5 (AR) | Pathogenic |
 RD_P426 | NDD, dysmorphic features , macrocephaly | ANKRD11; NM_013275, c.3882_3885dupAGAC, p.(Ser1296ArgfsTer5) | N.i. | Heterozygous | #148050 KBG syndrome (AD) | Likely Pathogenic |
Four SNVs detected with HPO terms-generated in silico gene panel | ||||||
 RD_P427 | NDD, hypotonia, dysmorphic features | TBCK, NM_033115, c.469+1G>A;469+1G>A | Paternal/ Maternal | Homozygous | #616900 Infantile hypotonia with psychomotor retardation and characteristic facies 3 (AR) | Pathogenic |
 RD_P428 | Arthrogryposis, dysmorphic features | ECEL1, NM_004826, c.494T>C, p.(Leu165Pro) ECEL1, NM_004826, c.2228G>T, p.(Arg743Met) | Not maternal | Compound heterozygous | #615065 Distal arthrogryposis type 5D (AR) | VUS |
Maternal | ||||||
 RD_P429 | Hypotonia, hearing loss | ACOX1, NM_004035, c.1729-1G>A | Paternal/Maternal | Homozygous | #264470 Peroxisomal acyl-CoA oxidase deficiency (AR) | Likely pathogenic |
 RD_P430 | Hypertrophic cardiomyopathy, severe anemia, respiratory failure | SPTA1, NM_003126, c.83G>A, p.(Arg28His) SPTA1, NM_003126, c.47854delG, p.(Arg1595Lysfs*38) | Paternal | Compound heterozygous | #270970 Spherocytosis type 3 (AR) | Pathogenic |
Maternal | ||||||
Repeat expansions detected by WGS | ||||||
 RD_P431 | Hypotonia, ASD, metabolic acidosis | ATXN7, STR | N.i. | Heterozygous | #164500 Spinocerebellar ataxia 7 (AD) | Pathogenic |
Uniparental isodisomy validated by WGS | ||||||
 RD_P432 | Hypotonia, dysmorphic features | Maternal UPD 15 (isodisomy) | N.a. | N.a. | #176270 Prader-Willi syndrome (AD) | Pathogenic |