Table 3.
Seven rare pathogenic CNVs and their candidate genes information.
| Case number/Sex/ CNV | Genes in the region | Known or candidate gene (s) for ID/GDD or EP/both | Associated diseases and mode of inheritance | RVIS (% of MIG) | Gene expression studies | CNV Reported in literature | Classification |
|---|---|---|---|---|---|---|---|
| 1/M De novo 19q13.2 deletion (333 Kb) | 11 RefSeq genes including ATP1A3, ERF | ATP1A3 | Alternating hemiplegia of childhood 2 (OMIM 614820) (AD) | −1.53 (3.37%) | High expression in neural tissues | Yes | P |
| 3/F Unknown inheritance 10q11.23-q22.1 deletion (21 Mb) | 154 RefSeq genes including ANK3. | ANK3 | Mental retardation, autosomal recessive, 37(OMIM 615493) (AR) | −3.5 (0.33%) | Medium expression in neural tissues. | No | P |
| 4/F Unknown inheritance Xp11.4-p11.3 deletion (2.14 Mb) | 15 RefSeq genes including CASK | CASK | Mental retardation and microcephaly with pontine and cerebellar hypoplasia(MICPCH) (OMIM 300749) (XLD): Mental retardation, with or without nystagmus (OMIM 300422) (XLD): FG syndrome 4 (OMIM 300422) (XLD). | −0.715 (14.4%) | Medium expression in neural tissues | No | P |
| 6/F Unknown inheritance 6q25.3-q25.3 del (240 Kb) | 2 RefSeq genes including ARID1B | ARID1B | Coffin-Siris syndrome 1(OMIM 135900) (AD) | −2.62 (0.8%) | High expression in neural Tissues | Yes | P |
| 10/M De novo 10q23.31-q24.33 duplication (14.82Mb) | 245 RefSeq genes, including C10orf2, CNNM2, and LGI1. | C10orf2, CNNM2, LGI1 | Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) (OMIM 271245) (AR): Hypomagnesemia, seizures, and mental retardation. (OMIM 616418) (AR,AD): Epilepsy, familial temporal lobe, 1 (OMIM 600512) (AD). | −0.78 (12.97%) −0.98 (8.75%) −0.71 (14.4%) | High expression in neural tissues | No | P |
| 22/M Unknown inheritance 8p21.2-p21 del (10.8Mb) | 106 RefSeq genes including CHRNA2 | CHRNA2 | Epilepsy, nocturnal frontal lobe, type 4 (OMIM 610353) (AD). | −0.753 (13.67%) | Low expression in neural tissues | Yes | P |
| 24/M De novo 8p23.3-p23.2 deletion (5.57 Mb) | 20 RefSeq genes including CLN8 | CLN8 | Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (OMIM 610003) (AR). | −0.14 (43.77%) | Medium expression in neural tissues | Yes | P |
M, male; F, female; AD, autosomal dominant; AR, autosomal recessive; CNV, copy number variation; ID, intellectual disability; GDD, global developmental delay; EP, epilepsy; MIG, most intolerant genes; RefSeq, reference sequence; RVIS, Residual Variation Intolerance Score; OMIM, Online Mendelian Inheritance in Man; MRI, magnetic resonance imaging; NIL, nothing.