Table 3.
Causative variants identified.
| Phenotype | Degree | Gene | Transcript | Variant 1 | Class | Variant 2 | Class | OMIM phenotype |
|---|---|---|---|---|---|---|---|---|
| Isolated SNHL | Severe | GJB2 | NM_004004.5 | c.35del p.(Gly12Valfs*2) | P | Homozygous | 220290 deafness, autosomal recessive 1A | |
| Isolated SNHL | Moderate | c.109G>A p.(Val37Ile) | P | Homozygous | ||||
| Isolated SNHL | Moderate | c.235del p.Leu79CysfsTer3 | P | Homozygous | ||||
| Isolated SNHL | Severe | c.35del p.(Gly12Valfs*2) | P | c.429G>A p.(Glu147Lys) | P | |||
| Isolated SNHL | Profound | c.71G>A p.(Trp24*) | P | Homozygous | ||||
| Isolated SNHL | Severe | c.167del p.(Leu56Argfs*26) | P | c.35del p.(Gly12Valfs*2) | P | |||
| Isolated SNHL | Severe | c.35del p.(Gly12Valfs*2) | P | Homozygous | ||||
| Isolated SNHL | Moderate | c.229T>C p.(Trp77Arg) | P | Homozygous | ||||
| Isolated SNHL | Mild | c.550C>T p.(Arg184Trp) | P | c.101T>C p.(Met34Thr) | P | |||
| Isolated SNHL | Profound | c.35del p.(Gly12Valfs*2) | P | c.167del p.(Leu56Argfs*26) | P | |||
| Isolated SNHL | Severe | c.101T>C p.(Met34Thr) | P | Homozygous | ||||
| Isolated SNHL | Profound | c.35del p.(Gly12Valfs*2) | P | Homozygous | ||||
| Isolated SNHL | Profound | c.35del p.(Gly12Valfs*2) | P | Homozygous | ||||
| Isolated SNHL | Moderate | c.101T>C p.(Met34Thr) | P | c.35del p.(Gly12Valfs*2) | P | |||
| Isolated SNHL | Profound | c.35del p.(Gly12Valfs*2) | P | Homozygous | ||||
| Isolated SNHL | Moderate | c.35del p.(Gly12Valfs*2) | P | c.101T>C p.(Met34Thr) | P | |||
| Isolated SNHL | Moderate | c.109G>A p.(Val37Ile) | P | Homozygous | ||||
| Isolated SNHL | Profound | c.71G>A p.(Trp24*) | P | Homozygous | ||||
| Isolated SNHL | Profound | c.71G>A p.(Trp24*) | P | c.35del p.(Gly12Valfs*2) | P | |||
| Isolated SNHL | Profound | c.35del p.(Gly12Valfs*2) | P | Homozygous | ||||
| Isolated SNHL | Profound | GJB2/6 | GJB2:c.35del p.(Gly12Valfs*2) | P | arr[hg19] 13q12.11(20,797,144–21,099,918) ×1 | 220290 deafness, digenic GJB2/GJB6 | ||
| Isolated SNHL | Severe | MY015A | NM_016239.3 | (NC_000017.10) c.10491 + 2T>C | LP | c.1137del p.(Tyr380Metfs*64) | P | 600316 deafness, autosomal recessive 3 |
| Isolated SNHL | Profound | c.9371dupA p.(Asn3124Lysfs*27) | LP | c.10250_10252delCCT p.(Ser3417del) | LP | |||
| Isolated SNHL | Moderate | c.1137del p.(Tyr380Metfs*64) | P | c.8183G>A p.(Arg2728His) | LP | |||
| Isolated SNHL | Profound | (NC_000017.10) c.6764 + 2T>A | LP | c.4351G>A p.(Asp1451Asn) | LP | |||
| Isolated SNHL | Severe | c.1185dupC p.(Glu396Argfs*36) | P | c.8162C>A p.(Thr2721Lys) | LP | |||
| Isolated SNHL | Severe | STRC | NM_153700.2 | c.4351C>T p.(Arg1451*) | LP | Homozygous | 603720 deafness, autosomal recessive 16 | |
| Isolated SNHL | Moderate | arr[hg19] 15q15.3(43,892,807–43,990,212) ×0 | ||||||
| Isolated SNHL | Moderate | arr[hg19] 15q15.3(43,892,807–43,939,659) ×0 | ||||||
| Isolated SNHL | Mild | arr[hg19] 15q15.3(43,892,807–43,895,643) ×0 | ||||||
| Isolated SNHL | Moderate | OTOA | NM_144672.3 | c.2207G>A p.(Gly736Glu) | VUS-FP | arr[hg19] 16p12.2(21,575,218–21,747,738) ×1 | 607039 deafness, autosomal recessive 22 | |
| Isolated SNHL | Moderate | TECTA | NM_005422.2 | c.5539T>C p.(ser1847Pro) de novo | LP | 601543 deafness, autosomal dominant | ||
| Isolated SNHL | Moderate | COCH | NM_004086.2 | c.1053C>A p.(Cys351Ter) | LP | Homozygous | 601369 deafness, autosomal dominant 9 | |
| Isolated SNHL | Moderate | LOXHD1 | NM_144612.6 | c.5885del p.(Thr1962Argfs*137) | LP | c.1759C>T p.(Arg587Trp) | VUS-FP | 613079 deafness, autosomal recessive 77 |
| Isolated SNHL | Moderate | PDZD7 | NM_001195263.1 | c.680G>A p.(Arg227His) | VUS-FP | Homozygous | 618003 deafness, autosomal recessive 57 | |
| Isolated SNHL | Moderate | OTOG | NM_001277269.1 | c.7454del p.(Arg2485Hisfs*77) | LP | Homozygous | 614945 deafness, autosomal recessive 18B | |
| Nystagmus, hypotonia, undescended testis | Profound | ESRRB | NM_004452.3 | c.520C>T p.(Arg174Cys) | VUS-FP | Homozygous | 608565 deafness, autosomal recessive 35 | |
| Dysplastic fingernails | Profound | GJB2 | NM_004004.5 | c.551G>A p.(Arg184Gln) | LP | 601544 deafness, autosomal dominant (Bart-Pumphrey) | ||
| DVA | Severe | SLC26A4 | NM_000441.1 | c.707T>C p.(Leu236Pro) | P | (NC_000007.13) c.1001 + 1G>A | P | 600791 deafness, AR with enlarged vestibular aqueduct OR 274600 Pendred syndrome |
| Prominent left endolymphatic sac | Profound | c.2168A>G p.(His723Arg) | P | Homozygous | ||||
| DVA | Mild | c.916dupG p.(Val306Glyfs*24) | P | (NC_000007.13) c.919-2 A>G | P | |||
| DVA | Severe | c.707T>C p.(Leu236Pro) | P | c.1226G>A p.(Arg409His) | P | |||
| Isolated SNHL | Moderate | c.1246A>C p.(Thr416Pro) | P | c.707T>C p.(Leu236Pro) | P | |||
| Isolated SNHL | Moderate | GATA3 | NM_001002295.1 | c.961T>A p.(Cys321Ser) de novo | P | 146255 hypoparathyroidism, SNHL and renal disease | ||
| Isolated SNHL | Severe | USH2A | NM_206933.2 | c.2299del p.(Glu767Serfs*21 | P | c.10699del p.(Leu3567*) | P | 276901 Usher syndrome type IIA |
| Hypotonia, DD, brachycephaly | Profound | MYO7A | NM_000260.3 | c.5422_5436del p.(Pro1808_Glu1812del) | VUS-FP | Homozygous | 276900 Usher syndrome type IB | |
| Isolated SNHL | Profound | MITF | NM_000248.3 | c.640C>T p.(Arg214*) de novo | P | 193510 Waardenburg syndrome type 2A | ||
| Transfusion dependant haemolytic anaemia | Profound | SPTB | NM_000347.5 | c.6041T>G p.(Phe2014Cys) | VUS-FP | Homozygous | 617948 anaemia, neontal haemolytic | |
| Syndactyly, synophrys, hirsutism, VSD | Severe | NIPBL | NM_133433.3 | c.188C>A p.(Ser63*) de novo | LP | 122470 Cornelia de Lange syndrome | ||
| Coloboma, Tetralogy of fallot, dysmorphism | Moderate | CHD7 | NM_017780.3 | c.6079C>T p.(Arg2027*) de novo | P | 214800 CHARGE syndrome | ||
| Microcephaly, DD, dysmorphism | Moderate | ERCC6 | NM_000124.3 | c.4177del p.(Met1393*) | LP | Homozygous | 133540 Cockayne syndrome | |
| Pulmonary valve stenosis | Moderate | PTPN11 | NM_002834.3 | c.329A>C p.(Glu110Ala) | LP | 163950 Noonan syndrome | ||
| Ectrodactyly | Severe | FGFR2 | NM_000141.4 | c.764G>A p.(Arg255Gln) | LP | Homozygous | Ectrodactyly | |
| Myopia, dysmorphism | severe | COL2A1 | NM_001844.4 | c.655G>A p.(Gly219Arg) | P | 108300 Stickler syndrome, type 1 | ||
| Dysmorphism, DD, multiple congenital anomalies | Severe | SDHA | NM_004168.2 | c.91C>T p.(Arg31*) | P | c.1781G>A p.(Arg594Lys) | LP | 256000 Leigh syndrome |
| Micrognathia, DD, dysmorphism | Severe | PIGN | NM_176787.4 | c.1379T>C p.(Leu460Ser) | VUS-FP | Homozygous | 614080 multiple congenital anomalies-hypotonia-seizures | |
| Horsehoe kidney, brain malformation, dysmorphic | Mild | SON | NM_138927.2 | c.1658del p.(Val553Glyfs*14) de novo | P | 617140 ZTTK syndrome | ||
| Pulmonary stenosis, posterior embryotoxin, IUGR | Moderate | ELN | arr[hg19] 7q11.23(72,722,981–74,129,824) ×1 de novo | 194050 Williams syndrome | ||||
| Cleft palate, dysmorphism, FTT, PDA | Moderate | TGFBR2 | arr[GRCh37] 3p24.2p22.3(29020250_33908346) ×1 de novo | 610168 Loeys-Dietz syndrone |
SNHL sensorineural hearing loss, DD developmental delay, DVA dilated vestibular aqueduct, IUGR intrauterine growth restriction, FTT failure to thrive, PDA patent ductus arteriosus, VSD ventricular septal defect