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Klinische FragestellungLeigh-Syndrom, Differentialdiagnose

Zusammenfassung

Kurzinformation

Umfassendes differentialdiagnostisches panel für nukleäre Gene, deren Veränderungen mit Leigh-Syndrom assoziiert sind, mit 34 Leitlinien-kuratierten sowie insgesamt 104 kuratierten Genen

ID
LP0420
Anzahl Gene
103 Akkreditierte Untersuchung
Untersuchte Sequenzlänge
58,7 kb (Core-/Core-canditate-Gene)
141,3 kb (Erweitertes Panel: inkl. additional genes)
Analyse-Dauer
auf Anfrage
Material
  • Chorionzotten (CVS)
  • EDTA-Blut (3-5 ml)
  • Fruchtwasser (nach AC)
  • Gewebeprobe
  • Mundschleimhaut (mind. zwei Abstrichtupfer)
  • Nabelschnurblut (NB)
Diagnostische Hinweise

NGS +

[[Sanger]]

 

Genpanel

Ausgewählte Gene

NameExon-Länge (bp)OMIM-GReferenz-Seq.Erbgang
ABAT1503NM_000663.5AR
AFG3L22394NM_006796.3AD, AR
AGK1269NM_018238.4AR
ANO101983NM_018075.5AR
APTX1029NM_175073.3AR
COQ21266NM_015697.9AR
COQ4798NM_016035.5AR
COQ61407NM_182476.3AR
COQ9957NM_020312.4AR
DGUOK834NM_080916.3AR
DNA23183NM_001080449.3AD
ETFDH1854NM_004453.4AR
FBXL41866NM_012160.5AR
GFER618NM_005262.3AR
MFN22274NM_014874.4AD, AR
MGME11035NM_052865.4AR
MPV17531NM_002437.5AR
OPA12883NM_015560.3AD, AR
PDSS11248NM_014317.5AR
PDSS21200NM_020381.4AR
POLG3720NM_002693.3AD, AR
RNASEH1869NM_002936.6AR
RRM2B1272NM_015713.5AR
SLC25A21897NM_001171170.2AR
SLC25A4897NM_001151.4AD, AR
SPG72388NM_003119.4AR, AD
SUCLA21392NM_003850.3AR
SUCLG11041NM_003849.4AR
SURF1903NM_003172.4AR
TFAM645NM_001270782.2AR
TK2705NM_001172643.1AR
TWNK2055NM_021830.5AD, AR
TYMP1449NM_001953.5AR
UTRN10302NM_007124.2n.k.
BCS1L1260NM_004328.5AR
BTD1572NM_001370658.1AR
CLPB2034NM_001258392.3AR, AD
COQ8A1944NM_020247.5AR
COX101332NM_001303.4AR
COX151167NM_004376.7AR
COX8A212NM_004074.3AR
DLAT1944NM_001931.5AR
DLD1530NM_000108.5AR
EARS21572NM_001083614.2AR
ECHS1873NM_004092.4AR
ETHE1765NM_014297.5AR
FARS21356NM_006567.5AR
FOXRED11461NM_017547.4AR
GFM12256NM_024996.7AR
GFM22436NM_001281302.2AR
GTPBP31575NM_133644.4AR
HIBCH1161NM_014362.4AR
IARS23039NM_018060.4AR
LIAS990NM_001278590.2AR
LIPT11122NM_001204830.2AR
LRPPRC4185NM_133259.4AR
MFF1029NM_020194.5AR
MRPS34749NM_023936.2AR
MTFMT1170NM_139242.4AR
MTRFR501NM_152269.5AR
NARS21434NM_024678.6AR
NDUFA101068NM_004544.4AR
NDUFA12438NM_018838.5AR
NDUFA2300NM_002488.5AR
NDUFA4246NM_002489.4AR
NDUFA91134NM_005002.5AR
NDUFAF2510NM_174889.5AR
NDUFAF4528NM_014165.4AR
NDUFAF5954NM_001039375.3AR
NDUFAF61002NM_152416.4AR
NDUFAF8228NM_001086521.2AR
NDUFS12184NM_005006.7AR
NDUFS21374NM_004550.5AR
NDUFS3795NM_004551.3AR
NDUFS4528NM_002495.4AR
NDUFS7642NM_024407.5AR
NDUFS8633NM_002496.4AR
NDUFV11368NM_007103.4AR
NDUFV2750NM_021074.5AR
NUBPL672NM_025152.3AR
PDHB1080NM_000925.4AR
PDHX1506NM_003477.3AR
PET100222NM_001171155.2AR
PET117248NM_001164811.2AR
PNPT12352NM_033109.5AR
POLG21458NM_007215.4AD, AR
PTCD32111NM_017952.6AR
SCO2801NM_005138.3AR
SDHA1995NM_004168.4AR
SDHAF1348NM_001042631.3AR
SERAC11965NM_032861.4AR
SLC19A31491NM_025243.4AR
SLC25A19963NM_001126121.2AR
SLC25A461257NM_138773.4AR
SLC39A81645NM_022154.5AR
SQOR1366NM_001271213.2AR
TACO1894NM_016360.4AR, Mi
TIMMDC1865NM_016589.4AR
TPK1585NM_001042482.2AR
TRMU1266NM_018006.5AR
TSFM1041NM_001172696.2AR
TTC19822NM_001271420.2AR
UQCRQ249NM_014402.5AR

Infos zur Erkrankung

Klinischer Kommentar

Das Leigh-Syndrom (LS) ist eine schwere neurologische Störung, die in der Regel im ersten Lebensjahr auftritt. Die Erkrankung ist durch fortschreitende psychomotorische Regression gekennzeichnet und führt in der Regel innerhalb von 2-3 Jahren zum Tod, oft aufgrund von Atemversagen. Bei einer kleinen Anzahl von Patienten treten die Symptome erst im Erwachsenenalter auf oder sie verschlimmern sich langsamer. Erste Anzeichen für LS sind in der Regel Erbrechen, Durchfall und Schluckstörungen sowie später Gedeihstörungen. Schwere Muskel- und Bewegungsprobleme sind ebenfalls häufig. Betroffene Personen können Hypotonie, Dystonie, Ataxie und periphere Neuropathie entwickeln. Viele Betroffene weisen eine Ophthalmoparese, Nystagmus oder eine Optikusatrophie auf. Schwere Atemprobleme sind häufig und können zu akutem Atemversagen führen. Einige Patienten entwickeln eine hypertrophe Kardiomyopathie und Laktazidose. Diese Symptome werden zum Teil durch Läsionen im Gehirn (Basalganglien, Kleinhirn, Hirnstamm) durch Demyelinisierung verursacht. LS kann durch Varianten in einem von ~100 verschiedenen Kern-Genen verursacht werden, ~20% der LS-Fälle weisen eine Variante in der mtDNA auf. Die meisten Gene, die mit LS in Verbindung gebracht werden, sind am Prozess der Energie-Erzeugung in den Mitochondrien beteiligt. Eines der am häufigsten veränderten Kern-Gene beim LS ist SURF1, das Vererbungsmuster ist in der Regel autosomal rezessiv. Da die diagnostische Ausbeute mittels Molekulargenetik bei LS-Fällen kaum mehr als 60% beträgt, kann ein negatives DNA-Testergebnis die klinische Diagnose nicht ausschließen.

Referenz: https://www.ncbi.nlm.nih.gov/books/NBK320989/

https://www.ncbi.nlm.nih.gov/books/NBK1173/

 

Synonyme
  • Alias: Leigh syndrome due to mitochondrial complex I-V deficiency
  • Allelic: Bjornstad syndrome (BCS1L)
  • Allelic: Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 (COX15)
  • Allelic: Cardiomyopathy, dilated, 1GG (SDHA)
  • Allelic: Cataract 38, AR (AGK)
  • Allelic: Charcot-Marie-Tooth disease, axonal, type 2EE (MPV14)
  • Allelic: Charcot-Marie-Tooth disease, axonal, types 2A2A + 2A2B (MFN2)
  • Allelic: Charcot-Marie-Tooth disease, type 4K (SURF1)
  • Allelic: Deafness, AR 70 (PNPT1)
  • Allelic: Deafness, AR 94 (NARS2)
  • Allelic: Deafness, AR 94 (NDUFA4)
  • Allelic: Deafness, mitochondrial, modifier of (TRMU)
  • Allelic: Fanconi renotubular syndrome 5 (NDUFAF2, NDUFAF6)
  • Allelic: GRACILE syndrome (BCS1L)
  • Allelic: Glaucoma, normal tension, susceptibility to (OPA1)
  • Allelic: Hereditary motor + sensory neuropathy VIA (MFN2)
  • Allelic: Leukoencephalopathy, progressive, with ovarian failure (AARS2)
  • Allelic: Liver failure, transient infantile (TRMU)
  • Allelic: Microcephaly, Amish type (SLC25A19)
  • Allelic: Multiple system atrophy, susceptibility to (COQ2)
  • Allelic: Myopia 6 (SCO2)
  • Allelic: Neuropathy, hereditary motor + sensory, type VIB (SLC25A46)
  • Allelic: Optic atrophy 1 (OPA1)
  • Allelic: Optic atrophy 12 (AFG3L2)
  • Allelic: Optic atrophy plus syndrome (OPA1)
  • Allelic: Paragangliomas 5 (SDHA)
  • Allelic: Perrault syndrome 5 (TWNK)
  • Allelic: Portal hypertension, noncirrhotic, 1 (DGUOK)
  • Allelic: Seckel syndrome 8 (DNA2)
  • Allelic: Spastic ataxia 5, AR (AFG3L2)
  • Allelic: Spinocerebellar ataxia 28 (AFG3L2)
  • 3-hydroxyisobutryl-CoA hydrolase deficiency (HIBCH)
  • 3-methylglutaconic aciduria with deafness, encephalopathy + Leigh-like syndrome (SERAC1)
  • 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement + neutropenia (CLPB)
  • Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (APTX)
  • Behr syndrome (OPA1)
  • Biotinidase deficiency (BTD)
  • Cataracts/growth hormone deficiency/sensory neuropathy/sensorineur. hear loss/skel. dyspl. (IARS2)
  • Coenzyme Q10 deficiency, primary, 1 (COQ2)
  • Coenzyme Q10 deficiency, primary, 2 (PDSS1)
  • Coenzyme Q10 deficiency, primary, 3 (PDSS2)
  • Coenzyme Q10 deficiency, primary, 4 (COQ8A)
  • Coenzyme Q10 deficiency, primary, 5 (COQ9)
  • Coenzyme Q10 deficiency, primary, 6 (COQ6)
  • Coenzyme Q10 deficiency, primary, 7 (COQ4)
  • Combined oxidative phosphorylation deficiency 1 (GFM1)
  • Combined oxidative phosphorylation deficiency 12 (EARS2)
  • Combined oxidative phosphorylation deficiency 13 (PNPT1)
  • Combined oxidative phosphorylation deficiency 14 (FARS2)
  • Combined oxidative phosphorylation deficiency 15 (MTFMT)
  • Combined oxidative phosphorylation deficiency 23 (GTPBT3)
  • Combined oxidative phosphorylation deficiency 24 (NARS2)
  • Combined oxidative phosphorylation deficiency 3 (TSFM)
  • Combined oxidative phosphorylation deficiency 32 (MRPS34)
  • Combined oxidative phosphorylation deficiency 39 (GFM2)
  • Combined oxidative phosphorylation deficiency 51 (PTCD3)
  • Combined oxidative phosphorylation deficiency 7 (MTRFR)
  • Combined oxidative phosphorylation deficiency 8 (AARS2)
  • Congenital disorder of glycosylation, type IIn (SLC39A8)
  • Dihydrolipoamide dehydrogenase deficiency (DLD)
  • Encephalopathy due to defective mitochondrial + peroxisomal fission 2 (MFF)
  • Ethylmalonic encephalopathy (ETHE1)
  • GABA-transaminase deficiency (ABAT)
  • Glutaric acidemia IIC (ETFDH)
  • Hyperglycinemia, lactic acidosis + seizures (LIAS)
  • Lacticacidemia due to PDX1 deficiency (PDHX)
  • Leigh syndrome (BCS1L, SDHA)
  • Leigh syndrome due to cytochrome c oxidase deficiency (COX15)
  • Leigh syndrome due to mitochondrial COX4 deficiency (COX10)
  • Leigh syndrome, due to COX IV deficiency (SURF1)
  • Lipoyltransferase 1 deficiency (LIPT1)
  • Mitochondrial DNA depletion syndrome 1, MNGIE type (TYMP)
  • Mitochondrial DNA depletion syndrome 11 (MGME1)
  • Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type, AD (SLC25A4)
  • Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type) AR (SLC25A4)
  • Mitochondrial DNA depletion syndrome 13, encephalomyopathic type (FBXL4)
  • Mitochondrial DNA depletion syndrome 14, encephalocardiomyopathic type (OPA1)
  • Mitochondrial DNA depletion syndrome 15, hepatocerebral type (TFAM)
  • Mitochondrial DNA depletion syndrome 16, hepatic type (POLG2)
  • Mitochondrial DNA depletion syndrome 16B, neuroophthalmic type (POLG2)
  • Mitochondrial DNA depletion syndrome 18 (SLC25A21)
  • Mitochondrial DNA depletion syndrome 2, myopathic type (TK2)
  • Mitochondrial DNA depletion syndrome 3, hepatocerebral type (DGUOK)
  • Mitochondrial DNA depletion syndrome 4A, Alpers type + 4B, MNGIE type (POLG)
  • Mitochondrial DNA depletion syndrome 5, encephalomyopathic +/- methylmalonic aciduria (SUCLA2)
  • Mitochondrial DNA depletion syndrome 6, hepatocerebral type (MPV14)
  • Mitochondrial DNA depletion syndrome 7, hepatocerebral type (TWNK)
  • Mitochondrial DNA depletion syndrome 8A, encephalomyopathic type with renal tubulopathy (RRM2B)
  • Mitochondrial DNA depletion syndrome 8B, MNGIE type (RRM2B)
  • Mitochondrial DNA depletion syndrome 9, encephalomyopathic type + methylmalonic aciduria (SUCLG1)
  • Mitochondrial complex I deficiency, nuclear type 1 (NDUFS4)
  • Mitochondrial complex I deficiency, nuclear type 13 (NDUFA2)
  • Mitochondrial complex I deficiency, nuclear type 15 (NDUFAF4)
  • Mitochondrial complex I deficiency, nuclear type 16 (NDUFAF5)
  • Mitochondrial complex I deficiency, nuclear type 17 (NDUFAF2, NDUFAF6)
  • Mitochondrial complex I deficiency, nuclear type 19 (FOXRED1)
  • Mitochondrial complex I deficiency, nuclear type 2 (NDUFS8)
  • Mitochondrial complex I deficiency, nuclear type 20 (ACAD9)
  • Mitochondrial complex I deficiency, nuclear type 21 (NUBPL)
  • Mitochondrial complex I deficiency, nuclear type 22 (NDUFA10)
  • Mitochondrial complex I deficiency, nuclear type 23 (NDUFA12)
  • Mitochondrial complex I deficiency, nuclear type 26 (NDUFA9)
  • Mitochondrial complex I deficiency, nuclear type 27 (MTFMT)
  • Mitochondrial complex I deficiency, nuclear type 3 (NDUFS7)
  • Mitochondrial complex I deficiency, nuclear type 31 (TIMMDC1)
  • Mitochondrial complex I deficiency, nuclear type 34 (NDUFAF8)
  • Mitochondrial complex I deficiency, nuclear type 4 (NDUFV1)
  • Mitochondrial complex I deficiency, nuclear type 5 (NDUFS1)
  • Mitochondrial complex I deficiency, nuclear type 6 (NDUFS2)
  • Mitochondrial complex I deficiency, nuclear type 7 (NDUFV2)
  • Mitochondrial complex I deficiency, nuclear type 8 (NDUFS3)
  • Mitochondrial complex II deficiency, nuclear type 2 (SDHAF1)
  • Mitochondrial complex III deficiency, nuclear type 1 (BCS1L)
  • Mitochondrial complex III deficiency, nuclear type 2 (TTC19)
  • Mitochondrial complex III deficiency, nuclear type 4 (UQCRQ)
  • Mitochondrial complex IV deficiency (COX10)
  • Mitochondrial complex IV deficiency, nuclear type 12 (PET100)
  • Mitochondrial complex IV deficiency, nuclear type 15 (COX8A)
  • Mitochondrial complex IV deficiency, nuclear type 19 (PET117)
  • Mitochondrial complex IV deficiency, nuclear type 2 (SCO2)
  • Mitochondrial complex IV deficiency, nuclear type 21 (NDUFA4)
  • Mitochondrial complex IV deficiency, nuclear type 5, French-Canadian (LRPPRC)
  • Mitochondrial complex IV deficiency, nuclear type 8 (TACO1)
  • Mitochondrial recessive ataxia syndrome; includes SANDO + SCAE (POLG)
  • Mitochondrial respiratory chain complex II deficiency (SDHA)
  • Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1)
  • Myopathy, mitochondrial progressive, with congenital cataract + developmental delay (GFER)
  • Pontocerebellar hypoplasia, type 1E (SLV25A46)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD (TWNK)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 2 (SLC25A4)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 4 (POLG2)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 5 (RRM2B)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 6 (DNA2)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 2 (RNASEH1)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 3 (TK2)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 4 (DGUOK)
  • Progressive external ophthalmoplegia, AD 1 (POLG)
  • Progressive external ophthalmoplegia, AR 1 (POLG)
  • Pyruvate dehydrogenase E1-beta deficiency (PDHB)
  • Pyruvate dehydrogenase E2 deficiency (DLAT)
  • Sengers syndrome (AGK)
  • Spastic paraplegia 55, AR (MTRFR)
  • Spastic paraplegia 7, AR (SPG7)
  • Spastic paraplegia 77, AR (FARS2)
  • Spinocerebellar ataxia, AR 10 (ANO10)
  • Sulfide:quinone oxidoreductase deficiency (SQOR)
  • Thiamine metabolism dysfunction syndrome 2, biotin-/thiamine-responsive encephalopathy 2 (SLC19A3)
  • Thiamine metabolism dysfunction syndrome 4, progressive polyneuropathy type (SLC25A19)
  • Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (TPK1)
Erbgänge, Vererbungsmuster etc.
  • AD
  • AR
  • Mi
  • n.k.
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatik und klinische Interpretation

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