Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2-Reference-Cited by-同舟云学术

Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2

Published:2019-10-29 Issue:1 Volume:10 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Corbett Mark A.^ORCID,Kroes Thessa,Veneziano Liana^ORCID,Bennett Mark F.^ORCID,Florian Rahel,Schneider Amy L.^ORCID,Coppola Antonietta,Licchetta Laura,Franceschetti Silvana,Suppa Antonio^ORCID,Wenger Aaron,Mei Davide^ORCID,Pendziwiat Manuela,Kaya Sabine,Delledonne Massimo^ORCID,Straussberg Rachel,Xumerle Luciano^ORCID,Regan Brigid,Crompton Douglas,van Rootselaar Anne-Fleur^ORCID,Correll Anthony,Catford Rachael,Bisulli Francesca,Chakraborty Shreyasee,Baldassari Sara^ORCID,Tinuper Paolo,Barton Kirston,Carswell Shaun,Smith Martin,Berardelli Alfredo,Carroll Renee,Gardner Alison,Friend Kathryn L.,Blatt Ilan,Iacomino Michele,Di Bonaventura Carlo,Striano Salvatore,Buratti Julien^ORCID,Keren Boris,Nava Caroline,Forlani Sylvie,Rudolf Gabrielle^ORCID,Hirsch Edouard,Leguern Eric,Labauge Pierre,Balestrini Simona^ORCID,Sander Josemir W.,Afawi Zaid,Helbig Ingo,Ishiura Hiroyuki^ORCID,Tsuji Shoji^ORCID,Sisodiya Sanjay M.,Casari Giorgio^ORCID,Sadleir Lynette G.,van Coller Riaan^ORCID,Tijssen Marina A. J.^ORCID,Klein Karl Martin^ORCID,van den Maagdenberg Arn M. J. M.,Zara Federico,Guerrini Renzo^ORCID,Berkovic Samuel F.^ORCID,Pippucci Tommaso,Canafoglia Laura^ORCID,Bahlo Melanie^ORCID,Striano Pasquale^ORCID,Scheffer Ingrid E.^ORCID,Brancati Francesco^ORCID,Depienne Christel^ORCID,Gecz Jozef^ORCID

Abstract

Abstract Familial Adult Myoclonic Epilepsy (FAME) is characterised by cortical myoclonic tremor usually from the second decade of life and overt myoclonic or generalised tonic-clonic seizures. Four independent loci have been implicated in FAME on chromosomes (chr) 2, 3, 5 and 8. Using whole genome sequencing and repeat primed PCR, we provide evidence that chr2-linked FAME (FAME2) is caused by an expansion of an ATTTC pentamer within the first intron of STARD7. The ATTTC expansions segregate in 158/158 individuals typically affected by FAME from 22 pedigrees including 16 previously reported families recruited worldwide. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and STARD7 gene expression is not affected. These data, in combination with other genes bearing similar mutations that have been implicated in FAME, suggest ATTTC expansions may cause this disorder, irrespective of the genomic locus involved.

Funder

Department of Health | National Health and Medical Research Council

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

Link

http://www.nature.com/articles/s41467-019-12671-y.pdf

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