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IllnessSpastic paraplegia, autosomal recessive; differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Spastic Paraplegia, autosomal recessive, containing 7 core candidate genes and altogether 102 curated genes according to the clinical signs

ID
PP0040
Number of genes
87 Accredited laboratory test
Examined sequence length
24,5 kb (Core-/Core-canditate-Genes)
192,5 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS + X

[Sanger]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
C19orf12459NM_001031726.3AR, AD
CYP7B11521NM_004820.5AR
FA2H1119NM_024306.5AR
PNPLA63984NM_006702.5AR
SPG117332NM_025137.4AR
SPG72388NM_003119.4AR, AD
ZFYVE267620NM_015346.4AR
ADAR2796NM_001111.5AR
AFG3L22394NM_006796.3AR
AIMP1939NM_004757.4AR
ALDH18A12388NM_002860.4AR
ALDH3A21458NM_000382.3AR
ALS24974NM_020919.4AR
AMPD22478NM_001368809.2AR
AP4B12220NM_006594.5AR
AP4E13414NM_007347.5AR
AP4M11362NM_004722.4AR
AP4S1480NM_007077.5AR
AP5Z12424NM_014855.3AR
ARG1969NM_000045.4AR
ARL6IP1612NM_015161.3AR
ATP13A23543NM_022089.4AR
B4GALNT11437NM_001276468.2AR
BICD22568NM_001003800.2AD
CAPN12145NM_001198868.2AR
CYP27A11596NM_000784.4AR
CYP2U11635NM_183075.3AR
DARS11506NM_001349.4AR
DDHD12640NM_001160147.2AR
DDHD22136NM_015214.3AR
DSTYK2790NM_015375.3AR
ENTPD11554NM_001098175.2AR
ERLIN11047NM_006459.4AR
ERLIN21020NM_007175.8AR
FAR11548NM_032228.6AR, AD
FARS21356NM_006567.5AR
FBXO71332NM_001033024.2AR
FXN633NM_000144.5AR
GAD11785NM_000817.3AR
GALC2058NM_000153.4AR
GBA22784NM_020944.3AR
GCH1753NM_000161.3AR, AD
GJC21320NM_020435.4AR
GLRX5474NM_016417.3AR
GPT21572NM_133443.4AR
GRID23024NM_001510.4AR
HACE12730NM_020771.4AR
HIKESHI647NM_016401.4AR
HPDL1117NM_032756.4AR
IBA571071NM_001010867.4AR
KIF1A5073NM_004321.8AR, AD
KIF1C3312NM_006612.6AR
KLC22244NM_001134774.2AR
KLC41999
  • No OMIM-Gs linked
NM_138343.4AR
LYST11406NM_000081.4AR
MAG1806NM_001199216.2AR
MARS12703NM_004990.3AR
MARS21782NM_138395.4AR
MTPAP1749NM_018109.4AR
MTRFR501NM_152269.5AR
NDUFA12438NM_018838.5AR
NKX6-2837NM_177400.3AR
NSRP11995NM_001261467.2AR
NT5C21686NM_001134373.3AR
OPA3540NM_025136.4AR
PCYT21269NM_001184917.3AR
PGAP12769NM_024989.4AR
POLR3A4173NM_007055.4AR
POLR3K330NM_016310.5AR
RAB3GAP24182NM_012414.4AR
REEP2765NM_001271803.2AR, AD
RNASEH2B939NM_024570.4AR
SACS13740NM_014363.6AR
SARS21563NM_001145901.2AR
SERAC11965NM_032861.4AR
SLC1A41607NM_003038.5AR
SLC25A15906NM_014252.4AR
SLC25A461257NM_138773.4AR
SPART2001NM_015087.5AR
SPG21927NM_016630.7AR
STN11221NM_024928.5AR
TAF81109NM_138572.3AR
TECPR23804NM_001172631.3AR
TFG1203NM_006070.6AR
TMEM63C2456NM_020431.4AR
WDR45B1035NM_019613.4AR
WDR482034NM_020839.4AR

Informations about the disease

Clinical Comment

Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of monogenic neurological diseases caused by length-dependent degeneration of the corticospinal tract and posterior cortical strands and manifests itself with bilateral spasticity of the lower extremities, hyperreflexia and plantar reactions of the extensor muscles. HSPs can occur in infancy, childhood, adolescence or adulthood. Furthermore, cognitive impairment, ataxia, dysarthria, neuropathy or seizures can be important additional symptoms in more than half of the cases. Autosomal recessive HSP is very heterogeneous and new genes are being identified. New causes of autosomal recessive HSP can be restricted to a family or a single individual. Autosomal recessive HSP occurs in about 25%-30% of all HSP patients. An inconspicuous genetic finding still does not mean a reliable exclusion of the suspected clinical diagnosis.

(Basic diagnostic genes: ###; additional genes: ###)

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1509/

https://www.thelancet.com/action/showPdf?pii=S1474-4422%2819%2930235-2

 

Synonyms
  • Alias: Hereditary spastic paraplegia, HSP
  • Alias: Spastic paraplegia [SPG], AR
  • Allelic: Amyotrophic lateral sclerosis 5, juvenile (SPG11)
  • Allelic: Anemia, sideroblastic, 3, pyridoxine-refractory (GLRX5)
  • Allelic: Boucher-Neuhauser syndrome (PNPLA6)
  • Allelic: Charcot-Marie-Tooth disease, axonal, type 2X (SPG11)
  • Allelic: Combined oxidative phosphorylation deficiency 7 (C12orf65)
  • Allelic: Congenital anomalies of kidney + urinary tract 1 (DSTYK)
  • Allelic: Deafness, AR 119 (AFG2B)
  • Allelic: Hyperphenylalaninemia, BH4-deficient, B (GCH1)
  • Allelic: Hyperuricemia, pulmonary hypertension, renal failure + alkalosis (SARS2)
  • Allelic: Laurence-Moon syndrome (PNPLA6)
  • Allelic: Leukodystrophy, hypomyelinating, 2 (GJC2)
  • Allelic: Lymphatic malformation 3 (GJC2)
  • Allelic: Neurodegeneration with brain iron accumulation 4 (C19orf12)
  • Allelic: Oliver-McFarlane syndrome (PNPLA6)
  • Allelic: Spinocerebellar ataxia 28 (AFG3L2)
  • 3-methylglutaconic aciduria with deafness, encephalopathy + Leigh-like syndrome (SERAC1)
  • 3-methylglutaconic aciduria, type III (OPA3)
  • Aicardi-Goutieres syndrome 2 (RNASH2B)
  • Aicardi-Goutieres syndrome 6 (ADAR)
  • Allelic: Parkinson disease 5, susceptibility to (UCHL1)
  • Allelic; Spastic paraplegia 79A, AD (UCHL1)
  • Argininemia (ARG1)
  • Cataracts, spastic paraparesis, speech delay (FAR1)
  • Cerebral palsy, spastic quadriplegic, 1 (GAD1)
  • Cerebroretinal microangiopathy with calcifications + cysts 2 (STN1)
  • Cerebrotendinous xanthomatosis (CYP27A1)
  • Charcot-Marie-Tooth disease, axonal, type 2U (MARS1)
  • Chediak-Higashi syndrome (LYST)
  • Coenzyme Q10 deficiency, primary, 7 (COQ4)
  • Dystonia, DOPA-responsive (GCH1)
  • Friedreich ataxia (FXN GAA)
  • Gastrointestinal defects and immunodeficiency syndrome 2 (PI4KA)
  • Glycogen storage disease IV (GBE1)
  • Hengel-Maroofian-Schols syndrome (BCAS3)
  • Hereditary spastic paraplegia [MONDO:0019064, panelapp] (CCDC82)
  • Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome (SLC25A15)
  • Hypomyelination with brainstem + spinal cord involvement + leg spasticity (DARS1)
  • Krabbe disease (GALC)
  • Kufor-Rakeb syndrome (ATP13A2)
  • Leukodystrophy, hypomyel., 7, with/-out oligodontia and/or hypogonadotropic hypogonadism (POLR3A)
  • Leukodystrophy, hypomyelinating, 13 (HIKESHI)
  • Leukodystrophy, hypomyelinating, 21 (POLR3K)
  • Leukodystrophy, hypomyelinating, 3 (AIMP1)
  • Leukodystrophy, hypomyelinating, 4 (HSPD1)
  • Leukodystrophy, progressive, early childhood-onset (ACER3)
  • Martsolf syndrome 1 (RAB3GAP2)
  • Mast syndrome (SPG21)
  • Mental retardation, AR 42 (PGAP1)
  • Mitochondrial complex I deficiency, nuclear type 23 (NDUFA12)
  • Neurodevelopmental disorder [MONDO:0700092, panelapp] (CCDC82)
  • Neurodevelopmental disorder with hearing loss + spasticity (AFG2B)
  • Neurodevelopmental disorder with microcephaly + spastic paraplegia (GPT2)
  • Neurodevelopmental disorder with neuromuscular + skeletal abnormalities (NRCAM)
  • Neurodevelopmental disorder with progressive spasticity + brain white matter abnormalities (HPDL)
  • Neurodevelopmental disorder with spastic quadriplegia + brain abnorm. with/-out seizures (WDR45B)
  • Neurodevelopmental disorder with spasticity, seizures + brain abnormalities (NSRP1)
  • Neurodevelopmental disorder, motor impairment, no language, cerebral hypomyel., brain atr. (TAF8)
  • Neuropathy, hereditary motor + sensory, type VIB (SLC25A46)
  • Parkinson disease 15, AR (FBXO7)
  • Peroxisomal fatty acyl-CoA reductase 1 disorder (FAR1)
  • Pituitary adenoma 4, ACTH-secreting, somatic (USP8)
  • Polyglucosan body disease, adult form (GBE1)
  • Polymicrogyria, perisylvian, with cerebellar hypoplasia + arthrogryposis (PI4KA)
  • Pontocerebellar hypoplasia, type 1B (EXOSC3)
  • Pontocerebellar hypoplasia, type 1E (SLC25A46)
  • Progressive Spastic Paresis [panelapp] (SARS2)
  • Severe ID + global developmental delay, epilepsy [panelapp] (BLOC1S1)
  • Sjogren-Larsson syndrome (ALDH3A2)
  • Spastic ataxia 2, AR (KIF1C)
  • Spastic ataxia 3, AR (MARS2)
  • Spastic ataxia 4, AR (MTPAP)
  • Spastic ataxia 5, AR (AFG3L2)
  • Spastic ataxia 8, AR, with hypomyelinating leukodystrophy (NKX6-2)
  • Spastic ataxia 9, AR (CHP1)
  • Spastic ataxia, Charlevoix-Saguenay type (SACS)
  • Spastic paralysis, infantile onset ascending (ALS2)
  • Spastic paraplegia + psychomotor retardation with/-out seizures (HACE1)
  • Spastic paraplegia 11, AR (SPG11)
  • Spastic paraplegia 13, AD (HSPD1)
  • Spastic paraplegia 15, AR (ZFYVE26)
  • Spastic paraplegia 18, AR (ERLIN2)
  • Spastic paraplegia 23 (DSTYK)
  • Spastic paraplegia 26, AR (B4GALNT1)
  • Spastic paraplegia 28, AR (DDHD1)
  • Spastic paraplegia 30, AR (KIF1A)
  • Spastic paraplegia 35, AR (FA2H)
  • Spastic paraplegia 39, AR (PNPLA6)
  • Spastic paraplegia 43, AR (C19orf12)
  • Spastic paraplegia 44, AR (GJC2)
  • Spastic paraplegia 45, AR (NT5C2)
  • Spastic paraplegia 46, AR (GBA2)
  • Spastic paraplegia 47, AR (AP4B1)
  • Spastic paraplegia 48, AR (AP5Z1)
  • Spastic paraplegia 49, AR (TECPR2)
  • Spastic paraplegia 50, AR (AP4M1)
  • Spastic paraplegia 51, AR (AP4E1)
  • Spastic paraplegia 52, AR (AP4S1)
  • Spastic paraplegia 53, AR (VPS37A)
  • Spastic paraplegia 54, AR (DDHD2)
  • Spastic paraplegia 55, AR (MTRFR syn. C12orf65)
  • Spastic paraplegia 56, AR (CYP2U1)
  • Spastic paraplegia 57, AR (TFG)
  • Spastic paraplegia 5A, AR (CYP7B1)
  • Spastic paraplegia 61, AR (ARL6IP1)
  • Spastic paraplegia 62, AR (ERLIN1)
  • Spastic paraplegia 63, AR (AMPD2)
  • Spastic paraplegia 64, AR (ENTPD1)
  • Spastic paraplegia 7, AR (SPG7)
  • Spastic paraplegia 72, AR (REEP2)
  • Spastic paraplegia 74, AR (IBA57)
  • Spastic paraplegia 75, AR (MAG)
  • Spastic paraplegia 76, AR (CAPN1)
  • Spastic paraplegia 77, AR (FARS2)
  • Spastic paraplegia 78, AR (ATP13A2)
  • Spastic paraplegia 79B, AR (UCHL1)
  • Spastic paraplegia 82, AR (PCYT2)
  • Spastic paraplegia 83, AR (HPDL)
  • Spastic paraplegia 84, AR (PI4KA)
  • Spastic paraplegia 86, AR (ABHD16)
  • Spastic paraplegia 87, AR (TMEM63C)
  • Spastic paraplegia 9B, AR (ALDH18A1)
  • Spastic paraplegia, childhood, complicated [genereviews] (KLC4)
  • Spastic paraplegia, optic atrophy + neuropathy (KLC2)
  • Spastic tetraplegia, thin corpus callosum + progressive microcephaly (SLC1A4)
  • Spasticity, childhood-onset, with hyperglycinemia (GLRX5)
  • Spinocerebellar ataxia, AR 18 (GRID2)
  • Troyer syndrome (SPART)
  • Warburg micro syndrome 2 (RAB3GAP2)
Heredity, heredity patterns etc.
  • AD
  • AR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined