Table 3. Patients carrying small (likely) pathogenic CNVs (affecting <15 genes).
| Patient (Gender) | Agei | Phenotype | Cytoband | Start-End (kb) | Size (Mb) | Copy number | Origin | Num of Genes | Candidate Genes | Pathogenicity |
|---|---|---|---|---|---|---|---|---|---|---|
| MR_3670 (Male) | 12M | Growth retardation, microcephaly, cryptorchidism, hypotonia, open foramen ovale, left had joint deformity, elevated right side of sternum, eye vascular tumor | 16p13.3 | 3,710.7–3,941.9 | 0.23 | Loss | De novoii | 1 | CREBBP (Exonic) | Confirmed: Rubinstein-Taybi syndrome (OMIM:180849) |
| MR_211 (Female) | 1Y1M | Delayed psychomotor development with prominent speech delay, microcephaly, hypotonia, no hearing problem, stereotyped movement | Xp11.4 | 41,403.1- 41,513.6 | 0.11 | Loss | De novo | 3 | CASK (Exonic) | Confirmed: X-linked MR (OMIM:300749) |
| MR_452 (Male) | 5Y | Delay in motor development, epileptic seizures, facial dysmorphic features | Xp21.1 | 31,674.3- 31,762.8 | 0.09 | Loss | Inherited from mother | 1 | DMD (Exonic) | Confirmed: Duchenne muscular dystrophy (OMIM:310200); incidental finding |
| MR_410iii (Male) | 4Y5M | Global DD, macrocephaly, hypertonia; Eccentric and repetitive behavior, restricted interest, poor social communication. | 9q33.1 | 118,395.0–118,716.1 | 0.32 | Loss | Inherited from mother | 2 | TRIM32, ASTN2 | Confirmed: risk locus for autism and other neuro-developmental disorders89 |
| MR_3699 (Male) | 5Y | Microcephaly, speech problems, spastic movement | 2p16.3 | 50,990.3–51,066.3 | 0.08 | Loss | Inherited from mother | 1 | NRXN1 (Exonic) | Confirmed: risk locus a range of developmental disorders90 |
| MR_1194iv (Male) | Prenatal | Congenital absence of abdominal muscle, died within first month after birth | 1q21.1 | 145,037.9–145,537.2 | 0.50 | Gain | Inherited from mother | 3 | CHD1L, PRKAB2 | Probable: critical gene of 1q21.1 deletion/duplication syndrome27,28 |
| MR_1234 (Male) | 11M | Developmental delay, mild facial dysmorphic features. | 19p13.3 | 4,973.6–5,099.4 | 0.13 | Loss | De novo | 1 | KDM4B | Probable: De novo loss of function variants associated with autism46 |
| MR_496 (Male) | 1Y5M | Hyperactivities, feeding difficulty, sleeping problem, deficits in emotional behavior | 7q31.33 | 125,762.5–125,899.9 | 0.14 | Loss | Inherited from mother | 1 | GRM8 (Exonic) | Probable: Deletions associated with ADHD91 and reported in autism92 |
| MR_3861v (Male) | 2Y | Intellectual disability, language impairment, gross motor delay, facial dysmorphic features (flat nose, long philtrum), single palmar creases | 8p23.3 | 0–2,015.5 | 2.2 | Loss | De novo | 9 | DLGAP2 | Likely: De novo deletions identified in autism93 |
| MR_1117 (Male) | 7Y | Hyperactivity, short attention span, learning difficulties (speech delay, poor comprehension, memory weakness), facial dysmorphic features (long face, protruding eyes) | 8p21.3 | 22,169.5–22,817 | 0.65 | Gain | De novo | 10 | PPP3CC | Likely: Reported duplication carriers with mood disorder47 and schizophrenia48 |
| MR_3465 (Male) | 3Y10M | Gross motor delay since birth, intellectual disability, no limb abnormality | 7q21.3 | 95,097.5–95,870.5 | 0.77 | Loss | Inherited from mother | 2 | SLC25A3, DYNC1I1 | Likely: SHFM locus (OMIM:183600); reported deletion carriers with MR without SHFM69 |
CNVs of known genomic disorders are not shown in this table. ADHD: attention deficit hyperactivity disorder, SHFM: split-hand/foot malformation.
iAge at the time of sample DNA collection. Clinical features may also include the findings from patient follow-ups.
iiDe novo occurrence in this case is presumed based on fully penetrant phenotype.
iiiPatient MR_410 also carried a second large pathogenic deletion at 22q13 (SHANK3).
ivMothers of the patient MR_1194 reported stillbirth or miscarriages in her previous three pregnancies; fetuses also showed abdominal wall defects.
vPatient MR_3861 also carried a second large pathogenic duplication 2q35-q37 (26.7 Mb, 208 genes). Both the duplication and deletion extend to telomeres, likely caused by a single unbalanced translocation. This case was a false negative in subtelomeric aberration screen.