Table 3:
Phenotype and inheritance pattern in children diagnosed (Dx) with genetic disorders by rWGS (N=17)
| Subject ID | Age | Sex | Dx Type | Phenotype | Diagnosis Name(s) | Gene | Inheritance | de novo or inherited | Variant Chromosomal (Chr)/Gene (c.) Coordinate(s) | HGVS nomenclature (c. and p.) | Zygosity | Minor Allele Frequency (MAF) in ExAC | HPO terms |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 6007 | 14 mo | F | C | Refractory complex partial epilepsy | Early infantile epileptic encephalopathy | PCDH19 | X-linked | de novo | chrX:88361395- 99758442 11.4 Mb deletion (Xq21.3q22.1) |
NA | heterozygous | NA | HP:0002373 |
| 6031 | 16 yr | F | C | Ventricular fibrillation, cardiac arrest | Catecholaminergic polymorphic ventricular tachycardia | RYR2 | AD | de novo | chr1:237632425 | c.1646C>T (p.Ala549Val) |
heterozygous | NF (not found) | HP:0001695 |
| 6052 | 3 yr | F | C | Complex partial epilepsy and developmental delay, new onset lactic acidosis | Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) | TANGO2 | AR | Inherited | chr22:20049207; chr22:20029260- 20062700×1 22q11.21 |
c.605+1G>A; del exons 3-9 |
compound heterozygous | 0.00032, NA |
HP:0011342 HP:0006846 HP:0030235 HP:0003128 |
| 6118a | 16 mo | M | C | Idiopathic pulmonary hypertension | Hereditary hemorrhagic telangiectasia, type 2 | ACVRL1 | AD | de novo | chr12:52314615 | c.1450C>T (p.Arg484Trp) |
heterozygous | NF | HP:0002092 |
| 6147 | 4 mo | M | C | Bilateral sensorineural hearing loss, transaminitis, anemia, new onset lethargy | Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) | TRNT1 | AR | Inherited | chr3:3182294 | c.443C>T (p.Ala148Val) |
homozygous | 0.00002 | HP:0002910 HP:0003128 HP:0008619 HP:0001935 |
| 6153a | 5 yr | F | C | Hypoparathyroidism, hypocalcemic status epilepticus | Autoimmune polyendocrinopathy syndrome, type I | AIRE | AR | Inherited | chr21:45706575; chr21:45713043 |
c.268T>C (p.Tyr90His); c.1265delC (p.Pro422LeufsTer58) |
compound heterozygous | NF, 0.00003 |
HP:0000829 HP:0002901 |
| 6159a | 5 yr | F | P | Pan serositis (ascites, peritonitis, pleural effusion, pericardial effusion), glomerulonephritis | Thin basement membrane nephropathy/ Alport syndrome | COL4A4 | AD | Inherited | chr2:227872828 |
c.4715C>T (p.Pro1572Leu) |
heterozygous | 0.00014 | HP:0000123 HP:0001903 HP:0003256 HP:0012115 HP:0031123 |
| 6180a | 19 mo | M | C | Ecthyma gangrenosum, sepsis | Agammaglobulinemia, X-linked | BTK | X-linked | de novo | chrX: 100615605 | c.726dupT (p.Ile243TyrfsTer15) |
heterozygous | NF | HP:0002721 HP:0001875 HP:0003256 HP:0010703 HP:0100806 |
| 6183 | 5 mo | M | C | Hypotonia, hypopnea, failure to thrive, and abnormal eye movements | Rett syndrome | MECP2 | X-linked | de novo | chrX:153296525 | c.789dupC (p.Gly264ArgfsTer7) |
heterozygous | NF | HP:0001319 HP:0040213 |
| 6193 | 22 mo | F | C | Distal arthrogryposis, developmental delay, apnea | Congenital contractures of the limbs and face, hypotonia, developmental delay (CLIFAHDD) | NALCN | AD | de novo | chr13:101828691 | c.1799A>G (p.Asp600Gly) |
heterozygous | NF | HP:0001263 HP:0005684 |
| 6205 | 11 yr | M | P | Wilms tumor, mental retardation, seizures | Mental retardation, autosomal recessive | PUS3 | AR | Inherited | chr11:125766179 | c.1A>G (p.Met1?) |
homozygous | 0.00002 | HP:0001249 HP:0000252 HP:0001003 HP:0002667 HP:0004322 |
| 6207a | 9 mo | M | C | Spontaneous intracranial hemorrhage | Factor XIIIA deficiency | F13A1 | AR | Inherited | chr6:6182326 | c.1352_1353delAT (p.His451ArgfsTer29) |
homozygous | NF | HP:0001048 HP:0001269 |
| 7002 | 10 yr | M | C | Ventricular fibrillation, cardiac arrest | Long QT syndrome, type 1 | KCNQ1 | AD | Inherited | chr11:2591949 | c.573_577delGCGCT (p.Arg192CysfsTer91) |
heterozygous | 0.00003 | HP:0001657 |
| 7004 | 14 yr | M | C | Ventricular fibrillation, cardiac arrest, hypertrophic cardiomyopathy | Cardiomyopathy, hypertrophic | MYH7 | AD | Inherited | chr14:23900677 | c.746G>A (p Arg249Gln) |
heterozygous | NF | HP:0001639 |
| 7031 | 5 yr | F | C | Refractory epilepsy, intermittent R hemiplegia | Alternating hemiplegia of childhood | ATP1A3 | AD | unknown | chr19:42490329 | c.449C>T (p.Ser150Phe) |
heterozygous | NF | HP:0001250 |
| 7039 | 11 mo | F | C | Apnea, hypotonia, global developmental delay, decreased cerebral white matter | Progressive encephalopathy with brain atrophy and thin corpus callosum | TBCD | AR | unknown | chr17:80763767; chr17:80828121 |
c.967C>T (p.Arg323Ter); c.1340C>T (p.Ala447Val) |
compound heterozygous | 0.00002, NF | HP:0002194 HP:0001601 HP:0002500 HP:0010314 HP:0012411 |
| 7043 | 17 yr | M | C | Ventricular fibrillation, cardiac arrest | Cardiomyopathy | ACTC1 | AD | Unknown | chr15:35086982 | c.28C>A (p.Leu10Met) |
heterozygous | 0.00003 | HP:0001638 HP:0001663 HP:0001695 HP:0004756 HP:0030149 |
C: Complete diagnosis; P: Partial diagnosis; AD: autosomal dominant; AR: autosomal recessive; XLD: X-linked dominant; NF: not found in ExAC.
a
Previously published cases (44, rS23-rS26)