Neurodegenerative disorders

In close collaboration with the Division of Molecular Neurology of the University Hospital Erlangen and the Department of Neurology and the Department of Neurosurgery of our University Hospital Regensburg, the Hehr Laboratory substantially contributed to the genetic and clinical characterization of SPG11, an autosomal recessive inherited form of complicated Hereditary Spastic Paraplegia (HSP) resulting from mutations in the Spatacsin gene. A special outpatient neurogenetics clinic is offered at our center since 2002, where we care for patients and their families with suspected inherited neurodegenerative disorders during the process of differential diagnosis and offer genetic counseling regarding carrier testing and family planning as well as genetic testing for a wide variety of neurdegenerative disorders.

We offer in our accredited laboratory:

  • pretest evaluation of your patients clinical information and cerebral MR imaging in order to develop an individual genetic testing strategy;
  • diagnostic genetic testing by Sanger sequencing as well as MLPA analysis
  • Linkage analysis for most autosomal recessive loci associated with complicated HSP
  • Next Generation Sequencing with our disease specific panel for Hereditary Spastic ParaplegiaHSP;
  • carrier testing.

All identified sequence alterations, relevant or potentially relevant for the clinical findings of your patient, are

  • confirmed by Sanger sequencing,
  • carefully assessed using our in house evaluation workflow including comparison with the human reference genome hg19, publically available and our own extensive mutation database as well as in silico prediction of functional consequences applying different algorithms,
  • rated and summarized in an individual medical report considering provided clinical data.

In addition to our NGS panel for Hereditary Spastic ParaplegiaHSP, covering 37 HSP-associated genes and 32 genes with clinically related movement disorders, we offer at our center genetic testing by Sanger sequencing, MLPA(+MLPA) and Linkage analysis (+Linkage) for:

Disease Disease
OMIM
Gene Gene
OMIM
Chromosomal
location

Neurodegenerative disorders

Andermann syndrome (+Linkage) 218000 KCC3 (SLC12A6) 604878 15q14
CADASIL syndrome (+MLPA) 125310 NOTCH3 600276 19p13.12
Brain small vessel disease, COL4A1-associated 607595 COL4A1 NM 120130 13q34
Cerebral cavernous malformations (+MLPA) 116860
603284
603285
CCM1 (KRIT1)
CCM2
CCM3 (PDCD10)
604214607929609118 7q21.2
7p13
3q26.1
Dementia, frontotemporal (+MLPA) 600274 MAPT 157140 17q21.31
Leukoencephalopathy, diffuse hereditary, with spheroids 221820 CSF1R 164770 17q21-q22
Metachromatic Leukencephalopathy 250100 ARSA 607574 22q13.33
Spinal and bulbar muscular atrophy of Kennedy 313200 AR 313700 Xq12
Pick disease (+MLPA) 172700 MAPT 157140 17q21.31
Supranuclear palsy, progressive (+MLPA) 601104 MAPT 157140 17q21.31
Spastic Paraplegia, hereditary (HSP)        
Panel complicated Spastic Paraplegia (37 HSP genes and further 32 clinically overlapping movement disorders)HSP pdf
autosomal-dominant        
Spastic Paraplegia 3 (+MLPA) 182600 ATL1 (Atlastin) HSP 606439 14q22.1
Spastic Paraplegia 4 (+MLPA) 182601 SPAST (Spastin) HSP 604277 2p22.3
Spastic Paraplegia 31 (+MLPA) 610250 SPG31 (REEP1) HSP 609139 2p11.2
autosomal-recessive        
Spastic Paraplegia 5 (+Linkage) 270800 CYP7B1 HSP 603711 8q12.3
Spastic Paraplegia 7 (+MLPA, Linkage) 607259 SPG7 (Paraplegin) HSP 602783 16q24.3
Spastic Paraplegia 11 (+MLPA, Linkage) 604360 SPG11 (Spatacsin) HSP 610844 15q21.1
Spastic Paraplegia 14 (only Linkage) 605229 SPG14 - Lokus 3q27-q28
Spastic Paraplegia 15 (+Linkage) 270700 ZFYVE26 (Spastizin) HSP 612012 14q24.1
Spastic Paraplegia 20 / Troyer syndrome (+Linkage) 275900 SPG20 (Spartin) HSP 607111 13q13.3
Spastic Paraplegia 21 / Mast syndrome (+Linkage) 248900 SPG21 (Maspardin) HSP 608181 15q22.31
Spastic Paraplegia 26 (only Linkage) 609195 SPG26 - Lokus 12p11.1-q14
X-linked        
Spastic Paraplegia 1, X-linked / MASA syndrome (+MLPA) 303350 L1CAM HSP 308840 Xq28

Related Publications of our group

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Two-hit mechanism in cerebral cavernous malformation? A case of monozygotic twins with a CCM1/KRIT1 germline mutation. Dammann P, Hehr U, Weidensee S, Zhu Y, Gerlach R, Sure U. Neurosurg Rev. 2013 Jul;36(3):483-6.

Edener U, Wöllner J, Hehr U, Kohl Z, Schilling S, Kreuz F, Bauer P, Bernard V, Gillessen-Kaesbach G, Zühlke C. Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation. Eur J Hum Genet. 2010 Aug;18(8):965-8.

Rudnik-Schöneborn S, Hehr U, von Kalle T, Bornemann A, Winkler J, Zerres K. Andermann syndrome can be a phenocopy of hereditary motor and sensory neuropathy--report of a discordant sibship with a compound heterozygous mutation of the KCC3 gene. Neuropediatrics. 2009 Jun;40(3):129-33.

Schüle R, Schlipf N, Synofzik M, Klebe S, Klimpe S, Hehr U, Winner B, Lindig T, Dotzer A, Riess O, Winkler J, Schöls L, Bauer P. Frequency and phenotype of SPG11 and SPG15 in complicated hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry. 2009 Dec;80(12):1402-4.

Bauer P, Winner B, Schüle R, Bauer C, Häfele V, Hehr U, Bonin M, Walter M, Karle K, Ringer TM, Riess O, Winkler J, Schöls L. Identification of a heterozygous genomic deletion in the spatacsin gene in SPG11 patients using high-resolution comparative genomic hybridization. Neurogenetics. 2009 Feb;10(1):43-8.

Hehr U, Bauer P, Winner B, Schule R, Olmez A, Koehler W, Uyanik G, Engel A, Lenz D, Seibel A, Hehr A, Ploetz S, Gamez J, Rolfs A, Weis J, Ringer TM, Bonin M, Schuierer G, Marienhagen J, Bogdahn U, Weber BH, Topaloglu H, Schols L, Riess O, Winkler J. Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia. Ann Neurol. 2007 Dec;62(6):656-65.

Olmez A, Uyanik G, Ozgül RK, Gross C, Cirak S, Elibol B, Anlar B, Winner B, Hehr U, Topaloglu H, Winkler J. Further clinical and genetic characterization of SPG11: hereditary spastic paraplegia with thin corpus callosum. Neuropediatrics. 2006 Apr;37(2):59-66.

Uyanik G, Elcioglu N, Penzien J, Gross C, Yilmaz Y, Olmez A, Demir E, Wahl D, Scheglmann K, Winner B, Bogdahn U, Topaloglu H, Hehr U, Winkler J. Novel truncating and missense mutations of the KCC3 gene associated with Andermann syndrome. Neurology. 2006 Apr 11;66(7):1044-8. Erratum in: Neurology. 2006 Oct 24;67(8):1528.

Winner B, Gross C, Uyanik G, Schulte-Mattler W, Lürding R, Marienhagen J, Bogdahn U, Windpassinger C, Hehr U, Winkler J. Thin corpus callosum and amyotrophy in spastic paraplegia--case report and review of literature. Clin Neurol Neurosurg. 2006 Oct;108(7):692-8.

Winner B, Uyanik G, Gross C, Lange M, Schulte-Mattler W, Schuierer G, Marienhagen J, Hehr U, Winkler J. Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus callosum in spastic gait gene 11 (SPG11). Arch Neurol. 2004 Jan;61(1):117-21.