Table 5.
Minimum recommended gene list for broad spectrum genetic testing for single-nucleotide variants associated with leukodystrophies and genetic leukoencephalopathies.
| Disease Name(s) | OMIM | Gene(s) |
|---|---|---|
| Hypomyelinating Leukodystrophies | ||
| Pol-III related disorders (4H leukodystrophy) | 607694 | POLR3A, POLR3B |
| Hypomyelinating leukodystrophy | 612438 | TUBB4A |
| Dystonia, type4 | ||
| HABC | ||
| Hypomyelination and congenital cataract (HCC) | 610532 | FAM126A |
| Pelizaeus-Merzbacher disease (PMD) | 312080 | PLP1 |
| Hypomyelinating leukodystrophy 2 (HLD2) | 608804 | GJC2 |
| Pelizaeus-Merzbacher-like disease 1 (PMLD1) | ||
| SOX10-associated PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy | 609136 | SOX10 |
| Waardenburg syndrome, and Hirschsprung disease | ||
| Other Leukodystrophies | ||
| X-linked Adrenoleukodystrophy (X-ALD) | 300100 | ABCD1 |
| Adult-onset leukodystrophy with neuroaxonal spheroids and pigmented glia (including Hereditary diffuse leukoencephalopathy with spheroids (HDLS) and Pigmentary orthochromatic leukodystrophy (POLD)) | 221820 | CSF1R |
| Aicardi-Goutieres Syndrome (AGS) | 615010 610333 610181 610329 612952 225750 |
ADAR1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, TREX1 |
| Alexander disease (AxD) | 203450 | GFAP |
| Adult onset autosomal dominant leukodystrophy (ADLD) | 169500 | LMNB1 |
| Canavan disease | 271900 | ASPA |
| Cerebrotendinosus Xanthomatosis (CTX) | 213700 | CYP27A1 |
| Chloride Ion Channel 2(ClC-2) related leukoencephalopathy with intramyelinic oedema | 615651 | CLCN2 |
| eIF2B related disorder (Vanishing WM Disease or CACH) | 603896 603896 603896 603896 603896 |
EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5 |
| Fucosidosis | 230000 | FUCA1 |
| Globoid cell leukodystrophy (Krabbe disease) | 245200 611722 |
GALC, PSAP |
| Hypomyelination wit Brainstem and Spinal Cord Involvement and Leg Spasticity (HBSL) | 615281 | DARS |
| Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) | 611105 | DARS2 |
| Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) | NA | EARS2 |
| Multiple sulfatase deficiency | 272200 | SUMF1 |
| Megalencephalic leukoencephalopathy with subcortical cysts (MLC) | 604004 613925 |
MLC1, HEPACAM |
| Metachromatic Leukodystrophy (MLD) | 607574 249900 |
ARSA, PSAP |
| Oculodentodigital dysplasia (ODDD) | 257850 | GJA1 |
| Polyglucosan Body Disease (PGBD) | 263570 | GBE1 |
| RNAse T2 deficient leukoencephalopathy | 612951 | RNASET2 |
| Sialic acid storage disease | 269920 | SLC17A5 |
| Sjogren Larsson syndrome | 270200 | ALDH3A2 |
| Progressive leukoencephalopathy with ovarian failure | 615889 | AARS2 |
| Other leukodystrophies: peroxisomal biogenesis disorders | ||
| Peroxisome biogenesis disorder 1A,B | 214100, 601539 | PEX1 |
| Peroxisome biogenesis disorder 5A,B | 614866, 614867 | PEX2 |
| Peroxisome biogenesis disorder 10A | 614882 | PEX3 |
| Peroxisome biogenesis disorder 4A,B | 614862, 614863 | PEX6 |
| Peroxisome biogenesis disorder 6A,B | 614870, 614871 | PEX10 |
| Peroxisome biogenesis disorder 3A,B | 614859, 266510 | PEX12 |
| Peroxisome biogenesis disorder 3A,B | 614872, 614873 | PEX26 |
| Other leukodystrophies: peroxisomal single enzyme beta oxidation deficiencies | ||
| D-bifunctional protein deficiency | 261515 | HSD17B4 |
| Sterol carrier protein 2 deficiency | 613724 | SCP2 |
| Leukoencephalopathy with dystonia and motor neuropathy | ||
| Peroxisomal acyl-coA-oxidase deficiency | 264470 | ACOX1 |
| Genetic leukoencephalopathies | ||
| L2-Hydroxyglutaric aciduria | 600721 | D2HGDH |
| 236792 | L2HGDH | |
| 615182 | SLC25A1 | |
| Cockayne syndrome; UV-sensitive syndrome | 609412 | ERCC6, ERCC8 |
| Deafness, dystonia, and cerebral hypomyelination | 300475 | BCAP31 |
| Trichothiodystrophy, nonphotosensitive | 234050 | MPLKIP |
| Trichotiodystrophy with hypersensitivity to sunlight | 601675 | ERCC2, ERCC3, GTF2H5 |
| Hypomyelinating leukodystrophy 3 | 260600 | AIMP1 |
| Hypomyelinating leukodystrophy 4 | 612233 | HSP60 |
| Mitochondrial HSP60 chaperonopathy | ||
| Global cerebral hypomyelination | 603667 | SLC25A12 |
| GM1-gangliosidosis | 230500 | GLB1 |
| GM2-gangliosidosis | 272800 | HEXA |
| Tay-Sachs disease | ||
| Infantile neuronal ceroid lipofuscinosis | 256730 | PPT1 |
| Mucolipidosis IV | 252650 | MCLON1 |
| Nasu-Hakola disease | 221770 | TYROBP |
| Dementia with bone cysts | ||
| Phosphoglycerate dehydrogenase deficiency | 601815 | PHGDH |
| Phosphoserine aminotransferase deficiency | 610992 | PSAT1 |
| Allan-Herndon-Dudley syndrome | 300523 | SLC16A2 |
| Monocarboxylate transporter 8 deficiency (MCT8) | ||
| Band-like intracranial calcification with simplified gyration and polymicrogyria | 251290 | OCLN |
| Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) | 125310 | NOTCH3 |
| Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) | 600142 | HTRA1 |
| Hereditary angiopathy with neuropathy, aneurysms and muscle cramps | 611773 | COL4A1 |
| Wilson disease | 277900 | ATP7B |
| Menkes disease | 300011 | ATP7A |
| Leukodystrophy, hypomyelinating, 4 | 612233 | HSPD1 |
| Spastic Paraplegia 13 | 605280 | |
| Fabry disease | 301500 | GLA |
| Familial hemophagocytic lymphohistiocytosis 5 | 613101 | STXBP2 |
| Familial hemophagocytic lymphohistiocytosis 3 | 608898 | UNC13D |
| Familial hemophagocytic lymphohistiocytosis 4 | 603552 | STX11 |
| Familial hemophagocytic lymphohistiocytosis 2 | 603553 | PRF1 |
| Lowe syndrome | 309000 | OCRL |
| Niemann-Pick type C2 | 601015 | NPC2 |
| Niemann-Pick type C1 | 257220 | NPC1 |
| Genetic leukoencephalopathies: mitochondrial disorders | ||
| Mitochondrial complex I disorders | 252010 | NDUFS1, NDUFS4, NDUFS7, NDUFS8, NDUFV1, NDUFS2, NDUFAF1 |
| Mitochondrial complex II disorders | 252011 | SDHA, SDHB, SDHAF1 |
| Mitochondrial complex III disorders | 124000 | BCS1L |
| Mitochondrial complex IV disorders | 256000 | SURF1 |
| 603644 | SCO1 | |
| 604377 | SCO2 | |
| 220110 | COX10 | |
| 256000 | COX15 | |
| 220110 | TACO1 | |
| Mitochondrial complex V disorders | 220110 | ATPAF2 |
| Glutaric Acidemia IIC | 231680 | ETFDH |
| Coenzyme Q10 deficiency, primary, 4 | 612016 | ADCK3 |
| Combined oxidative phosphorylation deficiency 1 | 609060 | GFM1 |
| Combined oxidative phosphorylation deficiency 2 | 610498 | MRPS16 |
| Combined oxidative phosphorylation deficiency 4 | 610678 | TUFM |
| Mitochondrial DNA depletion syndrome | 203700 | POLG |
| 4A, 4B and recessive ataxia syndrome | 613662 | |
| 607459 | ||
| Progressive external ophthalmoplegia with mitochondrial DNA deletions | 610131 | POLG2 |
| Mitochondrial DNA depletion syndrome 1 | 603041 | TYMP |
| Mitochondrial DNA depletion syndrome 5 | 612073 | SUCLA2 |
| Mitochondrial DNA depletion syndrome 7 | 271245 | C10ORF2 |
| Mitochondrial DNA depletion syndrome 8A | 604712 | RRM2B |
| Mitochondrial DNA depletion syndrome 12 | 615418 | SLC25A4 |
| Coenzyme Q10 deficiency, primary, 1 | 607426 | COQ2 |
| Coenzyme Q10 deficiency, primary, 5 | 614654 | COQ9 |
| Mitochondrial DNA depletion syndrome 3 | 251880 | DGUOK |
| Genetic leukoencephalopathies: hereditary spastic paraplegias | ||
| Spastic paraplegia 4 (SPG4) | 182601 | SPAST |
| Spastic paraplegia 5 (SPG5) | 270800 | CYP7B1 |
| Spastic paraplegia 7 (SPG7) | 607259 | SPG7 |
| Spastic paraplegia 11 (SPG11) | 604360 | SPG11 |
| Spastic paraplegia 15 (SPG15) | 270700 | ZFYVE26 |
| Spastic paraplegia 20 (SPG20) | 275900 | SPG20 |
| Spastic paraplegia 21 (SPG21) | 248900 | ACP33 |
| Spastic paraplegia 35 (SPG35) | 612319 | FA2H |
| Spastic paraplegia 56 (SPG56) | 615030 | CYP2U1 |
** 18q minus syndrome recommendations.