Table 2.
Clinical and genetic synopsis of patients with 22q11.2DS and a rare nonsynonymous variant of CDC45 gene
| Patient | 1 | 2 | 3 | 4 | 5 |
|---|---|---|---|---|---|
| Sex | Female | Female | Female | Male | Male |
| Age (years) | NA | 19 | 13 | 29 | NA |
| Ethnicity | Caucasian | Arab | Caucasian | Caucasian | Caucasian |
| Craniosynostosis and craniofacial anomalies | Bicoronal | Unicoronal | Bilateral cleft lip and palate | – | Multisutural craniosynostosis and posterior cleft palate |
| Limbs | Digitalized thumb, left preaxial PD | Digitalized thumb, patellar subluxation | – | – | Upper limb arthrogryposis, bilateral aberrantly placed and crowded toes |
| CHD | TA, AVSD | Aberrant LSCA | ASD | TA | DORV, VSD, vascular ring |
| Gastrointestinal | IM, anteriorly placed anus, right-sided anterior CDH | Severe dysphagia and g-tube | – | IA | Anteriorly placed anus, abdominal wall hernia |
| Genitourinary | Unicornuate uterus | – | – | Hypospadia | Cryptorchidsm |
| Short stature | – | Yes | – | Yes | – |
| Other | DF, accessory spleen | DF | DF, scoliosis | DF, scoliosis, occult SMCP | DF, sacral dimple, hypocalcemia |
| Status | Deceased—DOL 13 | Alive | Alive | Alive | Deceased—DOL 53 |
| del22q11.2 | FISH | FISH | MLPA—LCRA to D | FISH | SNP array—2.68 Mb deletion LCRA to D |
| Familial | Yes | No | No | No | Unknown |
| CDC45 variant | NM_001178010.2:c.847C>T:p (Arg283Cys) | NM_001178010.2:c.241G>A:p. (Val81Ile) | NM_001178010.2:c.241G>A:p. (Val81Ile) | NM_001178010.2:c.548C>G:p. (Ser183Cys) | NM_001178010.2:c.*36G>C |
| Variant position Hg19 | 22:19492931 | 22:19470249 | 22:19470249 | 22:19482035 | 22:19508038 |
| dbSNP | rs748698352 | rs13447203 | rs13447203 | rs151216373 | NA |
| Frequency gnomAD | 0.00002 | 0.01 | 0.01 | 0.0026 | NA |
| Prediction SIFT/PolyPhen-2/ MutationTaster/ Revel score | D | T | T | T | – |
| D | B | B | B | – | |
| D | D | D | N | – | |
| 0.707 | 0.01 | 0.01 | 0.01 | – | |
| Additional genetic findings | Trisomy 8 mosaicism | – | Pathogenic variant of SNAP29 | – | – |
ASD atrial septum defect, AVSD atrioventricular septal defect, B benign, CDH congenital diaphragmatic hernia, CHD congenital heart defect, D damaging/deleterious, DF dysmorphic features, DOL day of life, DORV double outlet right ventricle, FISH fluorescence in situ hybridization, IA imperforate anus, IM intestinal malrotation, LCR low copy repeats, LSCA left subclavian artery, MLPA multiplex ligation-dependent probe amplification, N nondamaging NA not applicable, PD polydactyly, SMCP submucosal cleft palate, SNP single-nucleotide polymorphism, T tolerated, TA truncus arteriosus, VSD ventricular septum defect.