Table 3.
Summary of genetic data.
| # | Disorders/Total | Gene | Number of patients | Zygosity (variant type) | NM number | Nucleotide change | Protein change | Status | Estimated MAF (x 105) in KSA* |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Metachromatic leukodystrophy (21) | ARSA | 9 | Homozygous (splicing) | NM_001085425.3 | c.1108-2A>G | p.? | Reported | 30 |
| 1 | Homozygous (missense) | NM_001085425.3 | c.883G>A | p.Gly295Ser | Reported | - | |||
| 1 | Homozygous (missense) | NM_001085425.3 | c.809T>C | p.Leu270Pro | Novel | - | |||
| PSAP | 10 | Homozygous (missense) | NM_002778.4 | c.722G>C | p.Cys241Ser | Reported | 68 | ||
| 2 | Leukoencephalopathy with vanishing white matter (VWM) (11) | EIF2B4 | 7 | Homozygous (missense) | NM_001318965.1 | c.1132C>T | p.Arg378Trp | Novel | 15 |
| EIF2B2 | 2 | Homozygous (missense) | NM_014239.4 | c.591C>G | p.Phe197Leu | Novel | - | ||
| EIF2B3 | 2 | Homozygous (missense) | NM_020365.5 | c.32G>T | p.Gly11Val | Reported | - | ||
| 3 | Peroxisome biogenesis disorders (PBD) (10) | PEX1 | 4 | Homozygous (nonsense) | NM_000466.3 | c.2176C>T | p.Gln726Ter | Reported | 11 |
| HSD17B4 | 3 | Homozygous (missense) | NM_000414.2 | c.2207T>A | p.Leu736His | Reported | - | ||
| PEX13 | 1 | Homozygous (start-loss) | NM_002618.3 | c.1A>G | p.Met1Val | Novel | 15 | ||
| PEX16 | 1 | Homozygous (splicing) | NM_057174.2, | c.113-1G>C | p.? | Novel | - | ||
| PEX6 | 1 | Homozygous (missense) | NM_000287.3 | c.1931G>A | p. Arg644Gln | Novel | 8 | ||
| RNASEH2B | 3 | Homozygous (missense) | NM_024570.4 | c.356A>G | p.Asp119Gly | Reported | 38 | ||
| 4 | Aicardi Goutieres syndrome (AGS) (9) | RNASEH2A | 1 | Homozygous (missense) | NM_006397.3 | c.202T>G | p.Ser68Ala | Novel | - |
| 1 | Homozygous (missense) | NM_006397.3 | c.557G>A | p.Arg186Gln | Reported | 118 | |||
| RNASEH2C | 1 | Homozygous (missense) | NM_032193.4 | c.202C>G | p.Leu68Val | Novel | 4 | ||
| IFIH1 | 1 | Heterozygous (missense) | NM_022168.4 | c.1850T>C | p.Ile617Thr | Novel | 8 | ||
| SAMHD1 | 1 | Homozygous (missense) | NM_015474.4 | c.428G>A | p.Arg143His | Reported | - | ||
| TREX1 | 1 | Heterozygous (missense) | NM_130384.3 | c.223G>A | p.Glu75Lys | Reported | - | ||
| 5 | Krabbe disease (7) | GALC | 1 | Homozygous (missense) | NM_000153.4 | c.916G>A | p.Ala306Thr | Reported | 4 |
| 1 | Homozygous (nonsense) | NM_000153.4 | c.396G>A | p.Trp132Ter | Reported | - | |||
| 1 | Homozygous (missense) | NM_000153.4 | c.1685T>C | p.Ile562Thr | Reported | - | |||
| 4 | Homozygous (missense) | NM_001201402.1 | c.1886C>G | p.Pro629Arg | Novel | - | |||
| 6 | Pelizaeus-Merzbacher-Like Disease (PMLD) (6) | GJC2 | 3 | Homozygous (frameshift) | NM_020435.4 | c.1134_1144del | p.Ala379GlyfsTer109 | Reported | - |
| 3 | Homozygous (frameshift) | NM_020435.4 | c.107delT | p.Ile36ThrfsTer3 | Novel | 8 | |||
| 7 | Megalencephalic Leukoencephalopathy with subcortical cyst (5) | MLC1 | 3 | Homozygous (frameshift) | NM_139202.3 | c.686_687delCAinsAG | p.Ser229Ter | Novel | - |
| 1 | Homozygous (splicing) | NM_139202.3 | c.177+1G>T | p.? | Reported | - | |||
| HEPACAM | 1 | Compound heterozygous (missense and splicing) | NM_152722.5 | c.416T>C, c.949-2A>G | p.Leu139Pro, p.? | Novel | -, 8 | ||
| 8 | Canavan Disease (4) | ASPA | 4 | Homozygous (frameshift) | NM_000049.4 | c.312_313delCA | p.Asp104GlufsTer2 | Novel | - |
| 9 | X-Linked Adrenoleukodystrophy (3) | ABCD1 | 3 | Homozygous (missense) | NM_000033.4 | c.542A>G | p.Tyr181Cys | Novel | - |
| 10 | Alexandar Disease (2) | GFAP | 1 | Heterozygous (missense) | NM_002055.5 | c.230A>G | p.Asn77Ser | Reported | - |
| 1 | Heterozygous (missense) | NM_002055.5 | c.715C>T | p.Arg239Cys | Reported | - | |||
| 11 | Pelizaeus-Merzbacher disease (PMD) (2) | PLP1 | 2 | Homozygous (missense) | NM_000533.5 | c.115G>A | p.Ala39Thr | Reported | - |
| 12 | Salla disease (2) | SLC17A5 | 1/2 | Homozygous (missense) | NM_012434.5 | c.406A>G | p.Lys136Glu | Novel | 8 |
| 1/2 | Homozygous (missense) | NM_012434.5 | c.116G>A | p.Arg39His | Novel | 19 | |||
| 13 | Oculodentodigital dysplasia (1) | GJA1 | 1 | Heterozygous (missense) | NM_000165.4 | c.125A>G | p.Glu42Gly | Novel | 4 |
*
Based on the numbers of carriers detected among 13,180 WES/WGS performed at CENTOGENE.