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

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

doi:10.1038/s41467-019-12671-y

Cited by 104 publications

(125 citation statements)

References 46 publications

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…For example, expansion of (CAG) n repeats in 13 different genes causes SCAs. Similarly, recently discovered expansions of (TTTTA) n (TTTCA) m repeats in the introns of five different genes are all linked to FAME (32,(67)(68)(69). Therefore, researchers have proposed toxic gain-offunction mechanisms, which could be either at the RNA or protein levels.…”

Section: From Expanded Dna Repeats To Diseasementioning

confidence: 99%

On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability

Khristich

Mirkin

2020

Journal of Biological Chemistry

197

239

View full text Add to dashboard Cite

Expansions of simple tandem repeats are responsible for almost 50 human diseases, the majority of which are severe, degenerative, and not currently treatable or preventable. In this review, we first describe the molecular mechanisms of repeat-induced toxicity, which is the connecting link between repeat expansions and pathology. We then survey alternative DNA structures that are formed by expandable repeats and review the evidence that formation of these structures is at the core of repeat instability. Next, we describe the consequences of the presence of long structure-forming repeats at the molecular level: somatic and intergenerational instability, fragility, and repeat-induced mutagenesis. We discuss the reasons for gender bias in intergenerational repeat instability and the tissue specificity of somatic repeat instability. We also review the known pathways in which DNA replication, transcription, DNA repair, and chromatin state interact and thereby promote repeat instability. We then discuss possible reasons for the persistence of disease-causing DNA repeats in the genome. We describe evidence suggesting that these repeats are a payoff for the advantages of having abundant simple-sequence repeats for eukaryotic genome function and evolvability. Finally, we discuss two unresolved fundamental questions: (i) why does repeat behavior differ between model systems and human pedigrees, and (ii) can we use current knowledge on repeat instability mechanisms to cure repeat expansion diseases?

show abstract

Section: From Expanded Dna Repeats To Diseasementioning

confidence: 99%

On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability

Khristich

Mirkin

2020

Journal of Biological Chemistry

197

239

View full text Add to dashboard Cite

show abstract

“…Giant somatosensory-evoked potential and long-latency cortical reflex can be detected by electromyography in patients with BAFME, which collectively support the cortical origin of the cortical tremor (3). Seven subtypes have been reported so far, including BAFME1 (8q24, OMIM 601068) (4), BAFME 2 (2p11.1-q12.2, OMIM 607876) (5), BAFME 3 (5p15.31-p15.1, OMIM 613608) (6), BAFME 4 (3q26.32-3q28, OMIM 615127) (7), BAFME 5 (1q32.1, OMIM 615400) (8), BAFME 6 (16p12.1, OMOM 618074) (4), and BAFME 7 (4q32.1, OMIM 618075) (4). Thus, BAFME showed genetic heterogeneity among different families.…”

Section: Introductionmentioning

confidence: 55%

“…Subsequently, TTTCA repeat insertions in an intron of YEATS2 in BAFME 4 was confirmed in a Thailand pedigree (7). ATTTC repeat expansions in STARD7 and unstable TTTTA/TTTCA expansions in MARCH6 were also found in European families (5,6). Here, we performed mutation analysis in a new BAFME family from central China and detected whether abnormal insertion of TTTTA and TTTCA expansions were associated with this BAFME pedigree.…”

Section: Introductionmentioning

confidence: 76%

TTTCA Repeat Expansion of SAMD12 in a New Benign Adult Familial Myoclonic Epilepsy Pedigree

et al. 2020

View full text Add to dashboard Cite

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disorder characterized by adult-onset cortical myoclonus with or without seizures. Recently, it was reported to be associated with intronic TTTTA/TTTCA expansions. To investigate whether these abnormal expansions are involved in our new pedigree from China, whole exome sequencing (WES) and repeat-primed polymerase chain reaction (RP-PCR) analysis were performed to detect potential mutation in pedigree members. Neither causal mutations cosegregated with the disease in the family nor any novel mutation was identified through WES, while an abnormal TTTCA expansion in SAMD12 was identified by RP-PCR and then proved to be cosegregated in the pedigree. All the 12 alive affected individuals (M/F = 4/8; average age = 46.7 years old, range from 27 to 66) showed typical characteristics of BAFME. In addition, maternal clinical anticipation was observed in six mother/child pairs. In conclusion, our study offered the evidence of intronic pentanucleotide expansions in SAMD12 from a new Chinese BAFME pedigree, which further confirmed the association between this expansion and the pathogenesis of BAFME.

show abstract

“…Recent discoveries have highlighted the importance of complex pathogenic repeat expansions involving non-reference insertions (Sato et al 2009;Seixas et al 2017;Ishiura et al 2018;Corbett et al 2019;Florian et al 2019;Yeetong et al 2019) . EHdn is currently the only method capable of discovering these expansions from BAM or CRAM files without the need for re-alignment of the supporting reads.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent discoveries have shown that many pathogenic repeats have complex structure and hence require more flexible methods. For instance: (a) REs causing spinocerebellar ataxia types 31 and 37, familial adult myoclonic epilepsy types 1, 2, 3, and 4, and Baratela-Scott syndrome (Sato et al 2009;Seixas et al 2017;Ishiura et al 2018;Corbett et al 2019;Florian et al 2019;Yeetong et al 2019;LaCroix et al 2019) occur within an inserted sequence relative to the reference; (b) expanded repeats recently shown to cause spinocerebellar ataxia, familial adult myoclonic epilepsy, and cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome have different composition relative to the reference STR (Sato et al 2009;Seixas et al 2017;Ishiura et al 2018;Corbett et al 2019;Florian et al 2019;Yeetong et al 2019) ; (c) Unverricht-Lundborg disease, a type of progressive myoclonus epilepsy, is caused by an expansion of a dodecamer (12-mer) repeat (Lalioti et al 1997) . None of the existing methods are capable of discovering all of these REs.…”

Section: Introductionmentioning

confidence: 99%

ExpansionHunter Denovo: A computational method for locating known and novel repeat expansions in short-read sequencing data

Dolzhenko

Bennett

Richmond

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

AbstractExpansions of short tandem repeats are responsible for over 40 monogenic disorders, and undoubtedly many more pathogenic repeat expansions (REs) remain to be discovered. Existing methods for detecting REs in short-read sequencing data require predefined repeat catalogs. However recent discoveries have emphasized the need for detection methods that do not require candidate repeats to be specified in advance. To address this need, we introduce ExpansionHunter Denovo, an efficient catalog-free method for genome-wide detection of REs. Analysis of real and simulated data shows that our method can identify large expansions of 41 out of 44 pathogenic repeats, including nine recently reported non-reference REs not discoverable via existing methods.ExpansionHunter Denovo is freely available at https://github.com/Illumina/ExpansionHunterDenovo

show abstract

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

Cited by 104 publications

References 46 publications

On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability

On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability

TTTCA Repeat Expansion of SAMD12 in a New Benign Adult Familial Myoclonic Epilepsy Pedigree

ExpansionHunter Denovo: A computational method for locating known and novel repeat expansions in short-read sequencing data

Contact Info

Product

Resources

About