Characteristics of the probands with breakpoints in genes without known/well-established association with human diseases
| Proband 1 | Proband 2 | Proband 3 | Proband 4 | Proband 5 | |
| Current age | 12 months | 21 years | 21 years | 16 years | 8 years |
| Karyotype | 46,XY,t(5;8)(q22;q13) | 46,XY,t(2;11)(q31;q21) | 46,XX,t(10;15)(q11.2;q13) | 46,XX,t(5,14)(q13.2;q24.3) | 46,XX,t(6;14)(p25;q13) |
| Implicated genes | EFNA5 | SLC4A10 | RET, BAHD1 | PPP2R5E | BLOC1S5-TXNDC5, TXNDC5 |
| ExAC pLI* | 0.889 | 0.003 | 0.991 (BAHD1) | 0.999 | 0 (TXNDC5) |
| DOMINO score# | 0.992 | 0.205 | 0.634 (BAHD1) | 0.86 | 0.138 (TXNDC5) |
| Gene function | erythropoietin-producing human hepatocellular (EPH)-related receptor, tyrosine kinase ligand | Na(+) dependent Cl-/HCO3- exchanger | Heterochromatin formation, gene silencing (BAHD1) | Protein phosphatase regulatory subunit | Endothelial protein disulfide isomerase |
| Gene expression (www.gtexportal.org) | Ubiquitously expressed with highest expression in: pituitary, minor salivary gland, vagina, cervix, aorta, brain. | Brain (only) | BAHD1 is ubiquitously expressed with highest expression in ovary, testis, thyroid, uterus, adrenal gland, fallopian tube. RET is expressed in brain, pituitary, colon and testis. | Ubiquitously expressed with highest expression in tibial arteries, brain, bladder, cervix, uterus, thyroid. | Ubiquitously expressed with lowest expression in brain. |
| WES | No | Yes | No | No | Yes |
| Physical parameters | small for gestational age (SGA), currently (2.4 years) weight <3rd centile; height 10th centile. | Normal | Low birth weight and disproportional length, currently normal. | Slightly underweight at birth; currently weight and height at 3rd–10th centiles. | None |
| ID/DD | Not observed | Moderate | Severe | Mild | Severe |
| Other neurological features | Hypotonia | Speech delay, hyperactivity, balance disorder, strange behaviour (sniffing) | Developmental regression, psychiatric disturbance, abnormal EEG, unspecific MRI changes | Personality disorder, self-mutilation | Lack of speech, lack of ambulation, seizures |
| Congenital anomalies | Bilateral cloudy cornea, supravalvular pulmonary stenosis, atrial septal defect, portosystemic venous shunt | Astigmatism | None | Retinal dystrophy, hyperopia, astigmatism | Microcephaly, corpus callosum hypoplasia |
| Dysmorphism | Square face, high forehead, bilateral epicanthic folds, sparse eyebrows, short and upturned nose, long and flat philtrum, narrow upper lip | Distal hand camptodactyly, unilateral transverse palmar crease | Large, soft and narrow hands with mild shortening of the metacarpals, long tapering fingers | Subtle hirsutism, low neck hairline, coarse face, rounded nasal tip, very broad thumbs (maternal feature), bilateral transverse palmar creases | None |
| Other | Not observed | Not observed | Urinary tract infection (UTI), septic ileus, Hirschsprung disease | aCGH: dup3p22pat, history of recurrent infections | None |
| References | 23–31 | 14 32–36 | 37–40 | 41–44 | 45–47 |
↵*pLI denotes the probability that a gene will be intolerant of loss-of-function mutations. The higher the pLI, the less tolerant the gene is of loss-of-function mutations.
# DOMINO score denotes the probability of a gene to harbor dominant mutations. The higher the score is, the more probable that the gene causes a disease with dominant inheritance.
aCGH, array comparative genomic hybridisation; DD, developmental delay; EEG, electroencephalography; ExAC, Exome Aggregation Consortium (http://exac.broadinstitute.org/); ID, intellectual delay; WES, whole-exome sequencing.