Healthy controls do not have pathogenic allele (TTTCA), but do have 9-20 benign motifs (TTTTA)⁶. Total allele size in probands spanned from 650-1035 repeats; an inverse relationship between allele size and age of onset was noted⁷. In one study it was proposed that pathogenicity only occurs when TTTCA is expanded⁵. RP-PCR can detect the pathogenic TTTCA insertion motif but does not adequately resolve complex TTTTA/TTTCA architecture⁸.

Mechanism

Unknown

Noted as unknown in literature⁴.

Detection

Long-range PCR followed by long-read sequencing has been used to size and determine structure [@pmid:40200849].

Year

2019⁹

Location in Gene

Intron 1

Gene Strand

Alleles

Ref. Motif

TTTTA

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

TTTCA

Pathogenic (gene)

ATTTC

Unknown (ref.)

ATGTT, TAGTT, TTTTG, TTTTT

Unknown (gene)

ATGTT, AGTTT, GTTTT, TTTTT

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

References

Direct supporting references for info on this page.

Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis.

Elisa,Vegezzi, Hiroyuki,Ishiura, D Cristopher,Bragg, David,Pellerin, Francesca,Magrinelli, Riccardo,Currò, Stefano,Facchini, Arianna,Tucci, John,Hardy, Nutan,Sharma, Matt C,Danzi, Stephan,Zuchner, Bernard,Brais, Mary M,Reilly, Shoji,Tsuji, Henry,Houlden, Andrea,Cortese

The Lancet. Neurology · 2024-07-01

pmid:38876750

Repeat expansion disorders.

Zhongbo,Chen, Huw R,Morris, James,Polke, Nicholas W,Wood, Sonia,Gandhi, Mina,Ryten, Henry,Houlden, Arianna,Tucci

Practical neurology · 2025-05-15

pmid:39349043

Familial cortical myoclonic tremor with epilepsy (FCMTE): Clinical characteristics and exclusion of linkages to 8q and 2p in a large French family.

E,Magnin, M,Vidailhet, C,Depienne, C,Saint-Martin, D,Bouteiller, E,LeGuern, E,Apartis, L,Rumbach, P,Labauge

Revue neurologique · 2009-07-18

pmid:19616813

4omim:613608

First clinical diagnosis of FAME3 via commercial Long-Read sequencing reveals mosaic repeat expansion in MARCHF6 gene.

B Lakshitha A,Perera, Russell,Stewart, Yutaka,Furuta, Kimberly M,Ezell, Lynette,Rives, Bethany,Nunley, Ashley,McMinn, Alyson,Krokosky, Serena,Neumann, Mary E,Koziura, Rizwan,Hamid, Joy D,Cogan, Thomas A,Cassini, Eric R,Gamazon, John A,Phillips Iii, Rory J,Tinker

Neurogenetics · 2025-08-11

pmid:40788430

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

7pmid:31664039, pmid:40788430

Novel, complex configurations of the

Mark F,Bennett, Mark A,Corbett, Thessa,Kroes, Laura,Canafoglia, Karen L,Oliver, Jillian M,Cameron, Neblina,Sikta, Jacob,Munro, Liam G,Fearnley, Kristina,Ibañez, Arianna,Tucci, Sanjay M,Sisodiya, Michael S,Hildebrand, Ingrid E,Scheffer, Carolina,Courage, Anna-Elina,Lehesjoki, Loretta,Giuliano, Giuseppe,Didato, Silvana,Franceschetti, Jozef,Gecz, Samuel F,Berkovic, Melanie,Bahlo

Brain communications · 2025-11-03

pmid:41268177

Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3.

Rahel T,Florian, Florian,Kraft, Elsa,Leitão, Sabine,Kaya, Stephan,Klebe, Eloi,Magnin, Anne-Fleur,van Rootselaar, Julien,Buratti, Theresa,Kühnel, Christopher,Schröder, Sebastian,Giesselmann, Nikolai,Tschernoster, Janine,Altmueller, Anaide,Lamiral, Boris,Keren, Caroline,Nava, Delphine,Bouteiller, Sylvie,Forlani, Ludmila,Jornea, Regina,Kubica, Tao,Ye, Damien,Plassard, Bernard,Jost, Vincent,Meyer, Jean-François,Deleuze, Yannick,Delpu, Mario D M,Avarello, Lisanne S,Vijfhuizen, Gabrielle,Rudolf, Edouard,Hirsch, Thessa,Kroes, Philipp S,Reif, Felix,Rosenow, Christos,Ganos, Marie,Vidailhet, Lionel,Thivard, Alexandre,Mathieu, Thomas,Bourgeron, Ingo,Kurth, Haloom,Rafehi, Laura,Steenpass, Bernhard,Horsthemke, Eric,LeGuern, Karl Martin,Klein, Pierre,Labauge, Mark F,Bennett, Melanie,Bahlo, Jozef,Gecz, Mark A,Corbett, Marina A J,Tijssen, Arn M J M,van den Maagdenberg, Christel,Depienne

Nature communications · 2019-10-29

pmid:31664039

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Novel, complex configurations of the

Brain communications · 2025-11-03

pmid:41268177

Targeted nanopore long-read sequencing panel for the molecular diagnosis of intronic expansion in familial adult myoclonic epilepsy.

Haruka,Urabe, Takashi,Nakajima, Satomi,Mitsuhashi, Kentaro,Ohta, Hidehiko,Fujinaka, Kiyoe,Goto, Aki,Sato

BMC medical genomics · 2025-11-11

pmid:41219789

A genome-wide approach for the discovery of novel repeat expansion disorders in the Undiagnosed Diseases Network cohort.

Sarah,Fazal, Harriet,Dashnow, Maike F,Dohrn, Jacquelyn,Raposo, Laurel,Hiatt, Matt C,Danzi, Isaac R L,Xu, Camilo,Toro, David R,Adams, Karen,Usdin, Bruce,Hayward, Shilpa Nadimpalli,Kobren, Shamil R,Sunyaev, Rebecca C,Spillmann, Vandana,Shashi, Adriana,Rebelo, Guney,Bademci, Mustafa,Tekin, Aaron R,Quinlan, Stephan,Zuchner

Genetics in medicine : official journal of the American College of Medical Genetics · 2025-05-22

pmid:40417743

Repeat Expansions with Small TTTCA Insertions in MARCHF6 Cause Familial Myoclonus without Epilepsy.

Theresa,Kühnel, Elsa,Leitão, Renate,Lunzer, Fabian,Kilpert, Sabine,Kaya, Claudia,Del Gamba, Kelly,Astudillo, Steven,Frucht, Marion,Simonetta-Moreau, Eric,Bieth, Iris,Unterberger, Giulietta Maria,Riboldi, Christel,Depienne

Movement disorders : official journal of the Movement Disorder Society · 2025-04-09

pmid:40200849

DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A.

Akane,Terasaki, Masayuki,Nakamura, Yuka,Urata, Hanae,Hiwatashi, Izumi,Yokoyama, Takeshi,Yasuda, Teiichi,Onuma, Kazumaru,Wada, Sunao,Kaneko, Rumiko,Kan, Shin-Ichi,Niwa, Ohiko,Hashimoto, Osamu,Komure, Yu-Ichi,Goto, Yuko,Yamagishi, Misa,Nakano, Yoshihiko,Furusawa, Akira,Sano

Journal of human genetics · 2020-10-10

pmid:33040085

Locus FAME3 MARCHF6

Disease

Locus

Alleles

gnomAD

References

Additional Literature