A PCR amplification method reveals instability of the dodecamer repeat in progressive myoclonus epilepsy (EPM1) and no correlation between the size of the repeat and age at onset

American Journal of Human Genetics
M D LaliotiS E Antonarakis

Abstract

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is a rare, autosomal recessive disorder characterized by onset at age 6-16 years, generalized seizures, incapacitating myoclonus, and variable progression to cerebellar ataxia. The gene that causes EPM1, cystatin B, encodes a cysteine proteinase inhibitor. Only a minority of EPM1 patients carry a point mutation within the transcription unit. The majority of EPM1 alleles contain large expansions of a dodecamer repeat, CCC CGC CCC GCG, located upstream of the 5' transcription start site of the cystatin B gene; normal alleles contain two or three copies of this repeat. All EPM1 alleles with an expansion were resistant to standard PCR amplification. To precisely determine the size of the repeat in affected individuals, we developed a detection protocol involving PCR amplification and subsequent hybridization with an oligonucleotide containing the repeat. The largest detected expansion was approximately 75 copies; the smallest was approximately 30 copies. We identified affected siblings with repeat expansions, of different sizes, on the same haplotype, which confirms the repeat's instability during transmissions. Expansions were observed directly; contractions wer...Continue Reading

References

Sep 4, 1992·Cell·R I Richards, G R Sutherland
Jul 22, 1991·FEBS Letters·V Turk, W Bode
Jul 15, 1994·American Journal of Medical Genetics·G LevinsonJ D Schulman
Sep 1, 1995·Electrophoresis·H Hummerich, H Lehrach
Jan 1, 1996·Annual Review of Neuroscience·H L Paulson, K H Fischbeck
Sep 1, 1997·Nature Genetics·M D LaliotiS E Antonarakis

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Citations

Jan 30, 2002·Pediatric Neurology·Kuriko Kagitani-ShimonoShintaro Okada
Nov 8, 2001·Journal of Biomolecular Structure & Dynamics·S S PataskarS K Brahmachari
Jan 16, 2002·Journal of Biomolecular Structure & Dynamics·P V JitheshR Joshi
Aug 14, 1999·Epilepsia·A E Lehesjoki, M Koskiniemi
Nov 22, 2007·Epilepsia·Tarja JoensuuOuti Kopra
Mar 8, 2008·Epilepsia·Reetta KälviäinenEsa Mervaala
Nov 16, 2013·Cellular and Molecular Neurobiology·Lisa UlbrichGabriella Augusti-Tocco
Feb 3, 2009·Epilepsy & Behavior : E&B·Edoardo FerlazzoPierre Genton
Sep 27, 2003·Epilepsia·Bruno MoulardAlain Malafosse
Mar 11, 2015·Epilepsia·Laura MumoliUNKNOWN Genetic Commission, Italian League Against Epilepsy
Oct 9, 2015·Epilepsy Currents·M Scott Perry
Jul 26, 2013·The International Journal of Neuroscience·Miljana KecmanovićStanka Romac
May 24, 2015·DNA Repair·Xiao-Nan Zhao, Karen Usdin
Dec 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·April L Darling, Vladimir N Uversky
Nov 13, 2007·Movement Disorders : Official Journal of the Movement Disorder Society·Nee K ChewKailash P Bhatia
Sep 22, 2017·Neurology·Laura CanafogliaSilvana Franceschetti
Jan 16, 2020·Paediatric Drugs·Gregory L Holmes
Apr 2, 2021·Brain : a Journal of Neurology·Takeshi MizuguchiNaomichi Matsumoto
Jun 5, 1999·Microbiology and Molecular Biology Reviews : MMBR·F Pâques, J E Haber

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