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:
|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
|Dementia, frontotemporal (+MLPA)||600274||MAPT||157140||17q21.31|
|Leukoencephalopathy, diffuse hereditary, with spheroids||221820||CSF1R||164770||17q21-q22|
|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|
|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|
|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|
|Spastic Paraplegia 1, X-linked / MASA syndrome (+MLPA)||303350||L1CAM HSP||308840||Xq28|
Related Publications of our groupmore...
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.