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IllnessNeuropathy, CMT2/HMSNII, axonal; differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Neuropathy, hereditary motor-sensory, axonal; type II, comprising 58 guideline-curated, 8 core genes, 7 core candidate genes and altogether 59 curated genes

ID
NP1230
Number of genes
42 Accredited laboratory test
Examined sequence length
27,0 kb (Core-/Core-canditate-Genes)
110,5 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

[[Sanger]]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
AARS12927NM_001605.3AD
BSCL21197NM_032667.6AD
GARS12220NM_002047.4AD
GDAP11077NM_018972.4AD, AR
GJB1852NM_000166.6XL
HARS11530NM_002109.6AD
HSPB1618NM_001540.5AD
KARS11940NM_001130089.2AR, AD
KIF1B5313NM_015074.3AD
MFN22274NM_014874.4AD, AR
MPZ747NM_000530.8AD
NEFL1633NM_006158.5AD, AR
PMP22483NM_000304.4AD
PNKP1566NM_007254.4AR
TRPV42616NM_021625.5AD
CHCHD10429NM_213720.3AD
DCAF81794NM_015726.4AD
DGAT21207NM_001253891.2AD
DHTKD12760NM_018706.7AD
DNAJB2834NM_001039550.2AR
DNM22613NM_001005360.3AD
DYNC1H113941NM_001376.5AD
HSPB8591NM_014365.3AD
IGHMBP22982NM_002180.3AR
KIF5A3099NM_004984.4AD
LMNA1995NM_170707.4AR
LRSAM12172NM_138361.5AD, AR
MARS12703NM_004990.3AD
MCM3AP5943NM_003906.5AR
MME2253NM_007289.4AD, AR
MTRFR501NM_152269.5AR
NAGLU2232NM_000263.4AD
NEFH3063NM_021076.4AD
PLEKHG53189NM_020631.6AR
RAB7A624NM_004637.6AD
SACS13740NM_014363.6AR
SLC25A461257NM_138773.4AR
SORD1074NM_003104.6AR
SPG117332NM_025137.4AR
TRIM22235NM_001130067.2AR
TTR444NM_000371.4AD
VCP2421NM_007126.5AD

Informations about the disease

Clinical Comment

Hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth (CMT) disorders and related neuropathies are a group of clinically and genetically heterogeneous conditions primarily affecting the peripheral nervous system with secondary muscle wasting and weakness. CMT is the most common inherited neuromuscular disorder, and patients with CMT and other HMSNs may present with many symptoms, with motor signs predominating over sensory symptoms in all age groups. Onset can occur in infancy, adolescence or throughout life with mild symptoms - even asymptomatic relatives can be detected in respective families. Motor nerve conduction velocities (NCV) distinguish two main types: CMT1 (demyelinating; NCV<35m/sec) and CMT2 (axonal; NCV>45m/sec). CMT neuropathy can be inherited either autosomal dominantly, recessively or X-linked (CMTX forms) and often occurs as a sporadic neuropathy. To date, over 60 different genetic loci have been associated with CMT1-4, CMTX and CMTdi (dominant intermediate type; NCV 35-45m/sec). Almost all of the relevant genes have been identified. These genes encode proteins involved in myelination, Schwann cell differentiation, axonal transport, endocytic recycling, mitochondrial function, protein translation, signal transduction, single-strand DNA break repair, and other processes. DNA diagnostic yields reported to date for all forms of CMT vary considerably from >20% to >60%, probably depending on the degree of clinical workup. Negative molecular genetic results by no means exclude clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1358/

 

Synonyms
  • Alias: CMT2, Charcot-Marie-Tooth type 2
  • Alias: HMSNII
  • Alias: Polyneuropathie
  • Allelic: Amyotrophic lateral sclerosis, susceptibility to (NEFH)
  • Allelic: Arts syndrome (PRPS1)
  • Allelic: Ataxia-oculomotor apraxia 4 (PNKP)
  • Allelic: Combined oxidative phosphorylation deficiency 6 (AIFM1)
  • Allelic: Combined oxidative phosphorylation deficiency 7 (MTRFR)
  • Allelic: Cortical dysplasia, complex, with other brain malformations 1 (TUBB3)
  • Allelic: Deafness, AR 89 (KARS1)
  • Allelic: Deafness, XL 1 (PRPS1)
  • Allelic: Deafness, XL 5 (AIFM1)
  • Allelic: Epileptic encephalopathy, early infantile, 29 (AARS)
  • Allelic: Fibrosis of extraocular muscles, congenital, 3A (TUBB3)
  • Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (CHCHD10)
  • Allelic: Glomerulosclerosis, focal segmental, 5 (INF2)
  • Allelic: Gout, PRPS-related (PRPS1)
  • Allelic: Hypomagnesemia, seizures + mental retardation 2 (ATP1A1)
  • Allelic: Microcephaly, seizures, developmental delay (PNKP)
  • Allelic: Mitochondrial complex IV deficiency, nuclear type 2 (SCO2)
  • Allelic: Myoclonus, intractable, neonatal (KIF5A)
  • Allelic: Myopathy, isolated mitochondrial, AD (CHCHD10)
  • Allelic: Myopia 6 (SCO2)
  • Allelic: Pheochromocytoma (KIF1B)
  • Allelic: Phosphoribosylpyrophosphate synthetase superactivity (PRPS1)
  • Allelic: Pontocerebellar hypoplasia, type 1E (SLC25A46)
  • Allelic: Spastic ataxia, Charlevoix-Saguenay type (SACS)
  • Allelic: Spastic paraplegia 10, AD (KIF5A)
  • Allelic: Spastic paraplegia 55, AR (MTRFR)
  • Allelic: Spastic paraplegia 57, AR (TFG)
  • Allelic: Spinal muscular atrophy, distal, AR, 4 (PLEKHG5)
  • Allelic: Spondyloepimetaphyseal dysplasia, XL, with hypomyelinating leukodystrophy (AIFM1)
  • Allelic: Usher syndrome type 3B (HARS1)
  • Basel-Vanagait-Smirin-Yosef syndrome (MED25)
  • Charcot-Marie-Tooth disease, DI C (YARS1)
  • Charcot-Marie-Tooth disease, DI D (MPZ)
  • Charcot-Marie-Tooth disease, DI E (INF2)
  • Charcot-Marie-Tooth disease, DI F (GNB4)
  • Charcot-Marie-Tooth disease, DI G (NEFL)
  • Charcot-Marie-Tooth disease, RI C (PLEKHG5)
  • Charcot-Marie-Tooth disease, RI D (COX6A)
  • Charcot-Marie-Tooth disease, RI, A (GDAP1)
  • Charcot-Marie-Tooth disease, RI, B (KARS1)
  • Charcot-Marie-Tooth disease, XLD, 6 (PDK3)
  • Charcot-Marie-Tooth disease, XLI [OMIM: CMTX1] (DRP2)
  • Charcot-Marie-Tooth disease, XLR, 5 (PRPS1)
  • Charcot-Marie-Tooth disease, axonal, type 2A2A (MFN2)
  • Charcot-Marie-Tooth disease, axonal, type 2A2B (MFN2)
  • Charcot-Marie-Tooth disease, axonal, type 2CC (NEFH)
  • Charcot-Marie-Tooth disease, axonal, type 2DD (ATP1A1)
  • Charcot-Marie-Tooth disease, axonal, type 2EE (MPV17)
  • Charcot-Marie-Tooth disease, axonal, type 2F (HSPB1)
  • Charcot-Marie-Tooth disease, axonal, type 2HH (JAG1)
  • Charcot-Marie-Tooth disease, axonal, type 2K (GDAP1)
  • Charcot-Marie-Tooth disease, axonal, type 2N (AARS)
  • Charcot-Marie-Tooth disease, axonal, type 2W (HARS1)
  • Charcot-Marie-Tooth disease, axonal, type 2Z (MORC2)
  • Charcot-Marie-Tooth disease, axonal, with vocal cord paresis (GDAP1)
  • Charcot-Marie-Tooth disease, type 1A (PMP22)
  • Charcot-Marie-Tooth disease, type 1B (MPZ)
  • Charcot-Marie-Tooth disease, type 1E (PMP22)
  • Charcot-Marie-Tooth disease, type 1F (NEFL)
  • Charcot-Marie-Tooth disease, type 2A1 (KIF1B)
  • Charcot-Marie-Tooth disease, type 2A1 [OMIM] (DGAT2)
  • Charcot-Marie-Tooth disease, type 2B2 (PNKP)
  • Charcot-Marie-Tooth disease, type 2D (GARS1)
  • Charcot-Marie-Tooth disease, type 2E (NEFL)
  • Charcot-Marie-Tooth disease, type 2I (MPZ)
  • Charcot-Marie-Tooth disease, type 2J (MPZ)
  • Charcot-Marie-Tooth disease, type 4A (GDAP1)
  • Charcot-Marie-Tooth neuropathy, XLD, 1 (GJB1)
  • Cowchock syndrome (AIFM1)
  • Dejerine-Sottas disease (MPZ, PMP22)
  • Developmental delay, impaired growth, dysmorphic facies + axonal neuropathy (MORC2)
  • Giant axonal neuropathy-1 (GAN)
  • Giant axonal neuropathy-2, AD (DCAF8)
  • Hereditary motor + sensory neuropathy VIA (MFN2)
  • Hereditary motor + sensory neuropathy, type IIc (TRPV4)
  • Hereditary motor and sensory neuropathy, Okinawa type (TFG)
  • Hereditary neuropathies [panelapp] (KIF5A, TTR, TUBB3)
  • Hereditary neuropathy [panelapp] (MTRFR)
  • Hereditary neuropathy [panelapp] (SACS)
  • Hereditary neuropathy [panelapp] (SCO2)
  • Hypomyelinating neuropathy, congenital, 2 (MPZ)
  • Infantile-onset multisystem neurologic, endocrine + pancreatic disease 2 (YARS1)
  • Mitochondrial DNA depletion syndrome 6, hepatocerebral type (MPV17)
  • Neuromyotonia and axonal neuropathy, AR (HINT1)
  • Neuronopathy, distal hereditary motor, type IIB (HSPB1)
  • Neuronopathy, distal hereditary motor, type VA (GARS1)
  • Neuronopathy, distal hereditary motor, type VIII (TRPV4)
  • Neuropathy, distal hereditary motor, type VA (BSCL2)
  • Neuropathy, hereditary motor + sensory, type VIB (SLC25A46)
  • Neuropathy, inflammatory demyelinating (PMP22)
  • Neuropathy, recurrent, with pressure palsies (PMP22)
  • Peripheral neuropathy, AR, with/-out impaired intellectual development (MCM3AP)
  • Roussy-Levy syndrome (MPZ, PMP22)
  • Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORD)
  • Spinal muscular atrophy, Jokela type (CHCHD10)
  • Spinal muscular atrophy, distal, AR, 5 (DNAJB2)
Heredity, heredity patterns etc.
  • AD
  • AR
  • XL
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

Test-Stärken

  • DAkkS-akkreditiertes Labor
  • EU-Richtlinie für IVD in Umsetzung
  • Qualitäts-kontrolliert arbeitendes Personal
  • Leistungsstarke Sequenzierungstechnologien, fortschrittliche Target-Anreicherungsmethoden und Präzisions-Bioinformatik-Pipelines sorgen für überragende analytische Leistung
  • Sorgfältige Kuratierung klinisch relevanter und wissenschaftlich begründeter Gen-Panels
  • eine Vielzahl nicht Protein-kodierender Varianten, die in unseren klinischen NGS-Tests mit erfasst werden
  • unser strenges Variantenklassifizierungsschema nach ACMG-Kriterien
  • unser systematischer klinischer Interpretations-Workflow mit proprietärer Software ermöglicht die genaue und nachvollziehbare Verarbeitung von NGS-Daten
  • unsere umfassenden klinischen Aussagen

Testeinschränkungen

  • Gene mit eingeschränkter Abdeckung werden gekennzeichnet
  • Gene mit kompletten oder partiellen Duplikationen werden gekennzeichnet
  • es wird angenommen, dass ein Gen suboptimal abgedeckt ist, wenn >90% der Nukleotide des Gens bei einem Mapping-Qualitätsfaktor von >20 (MQ>20) nicht abgedeckt sind
  • die Sensitivität der Diagnostik zur Erkennung von Varianten mit genannten Testeinschränkungen ist möglicherweise begrenzt bei:
  • Gen-Konversionen
  • komplexe Inversionen
  • Balancierte Translokationen
  • Mitochondriale Varianten
  • Repeat-Expansionen, sofern nicht anders dokumentiert
  • nicht kodierende Varianten, die Krankheiten verursachen, die von diesem Panel nicht mit abgedeckt werden
  • niedriger Mosaik-Status
  • Repeat-Blöcke von Mononukleotiden
  • Indels >50bp (Insertionen-Deletionen)
  • Deletionen oder Duplikationen einzelner Exons
  • Varianten innerhalb von Pseudogenen
  • die analytische Sensitivität kann geringer ausfallen werden, wenn die DNA nicht von amedes genetics extrahiert wurde

Laboratory requirement

  • Die in grün gezeigten Gene sind kuratiert und werden als Gen-Panel untersucht. Eine Erweiterung des Panels (blau gezeigte Gene, jeweils ebenfalls kuratiert) kann auf Anfrage erfolgen. Sofern unter "Erweitertes Panel" ein Minuszeichen angezeigt wird, sind nur Core-/Basis-Gene verfügbar.

  • Für die Anforderung einer genetischen Untersuchung senden Sie uns bitte die Krankheits-ID auf einem Überweisungsschein. Bitte die Material-Angabe beachten.

  • Für privat versicherte Patienten empfehlen wir einen Antrag auf Kostenübernahme bei der Krankenversicherung.

  • Die Untersuchung wird auch für Selbstzahler angeboten.