Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and SAMD12 intronic repeat expansion
© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy..
Objective: Our goal was to perform detailed clinical and genomic analysis of a large multigenerational Chinese family with 21 individuals showing symptoms of Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE) that we have followed for over 20 years.
Methods: Patients were subjected to clinical evaluation, routine EEG, and structural magnetic resonance imaging. Whole exome sequencing, repeat-primed PCR, long-range PCR, and PacBio sequencing were performed to characterize the disease-causing mutation in this family.
Results: All evaluated patients manifested adult-onset seizures and presented with progressive myoclonic postural tremors starting after the third or fourth decade of life. Seizures typically diminished markedly in frequency with implementation of antiseizure medications but did not completely cease. The electroencephalogram of affected individuals showed generalized or multifocal spikes and slow wave complexes. An expansion of TTTTA motifs with addition of TTTCA motifs in intron 4 of SAMD12 was identified to segregate with the disease phenotype in this family. Furthermore, we found that the mutant allele is unstable and can undergo both contraction and expansion by changes in the number of repeat motifs each time it is passed to the next generation. The size of mutant allele varied from 5 to 5.5 kb with 549-603 copies of TTTTA and 287-343 copies of TTTCA repeat motifs in this family.
Significance: Our study provides a detailed description of clinical progression of FCMTE symptoms and its management with antiseizure medications. Our method of repeat analysis by PacBio sequencing of long-range PCR products does not require high-quality DNA and hence can be easily applied to other families to elucidate any correlation between the repeat size and phenotypic variables, such as, age of onset, and severity of symptoms.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Epilepsia open - 6(2021), 1 vom: 02. März, Seite 102-111 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Yongxing [VerfasserIn] |
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| Links: |
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| Themen: |
33CM23913M |
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| Anmerkungen: |
Date Completed 19.10.2021 Date Revised 31.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1002/epi4.12450 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Zhou, Yongxing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and SAMD12 intronic repeat expansion |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 19.10.2021 | ||
| 500 | |a Date Revised 31.03.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. | ||
| 520 | |a Objective: Our goal was to perform detailed clinical and genomic analysis of a large multigenerational Chinese family with 21 individuals showing symptoms of Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE) that we have followed for over 20 years | ||
| 520 | |a Methods: Patients were subjected to clinical evaluation, routine EEG, and structural magnetic resonance imaging. Whole exome sequencing, repeat-primed PCR, long-range PCR, and PacBio sequencing were performed to characterize the disease-causing mutation in this family | ||
| 520 | |a Results: All evaluated patients manifested adult-onset seizures and presented with progressive myoclonic postural tremors starting after the third or fourth decade of life. Seizures typically diminished markedly in frequency with implementation of antiseizure medications but did not completely cease. The electroencephalogram of affected individuals showed generalized or multifocal spikes and slow wave complexes. An expansion of TTTTA motifs with addition of TTTCA motifs in intron 4 of SAMD12 was identified to segregate with the disease phenotype in this family. Furthermore, we found that the mutant allele is unstable and can undergo both contraction and expansion by changes in the number of repeat motifs each time it is passed to the next generation. The size of mutant allele varied from 5 to 5.5 kb with 549-603 copies of TTTTA and 287-343 copies of TTTCA repeat motifs in this family | ||
| 520 | |a Significance: Our study provides a detailed description of clinical progression of FCMTE symptoms and its management with antiseizure medications. Our method of repeat analysis by PacBio sequencing of long-range PCR products does not require high-quality DNA and hence can be easily applied to other families to elucidate any correlation between the repeat size and phenotypic variables, such as, age of onset, and severity of symptoms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a FCMTE | |
| 650 | 4 | |a SAMD12 | |
| 650 | 4 | |a epilepsy | |
| 650 | 4 | |a myoclonus | |
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| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
| 650 | 7 | |a SAMD12 protein, human |2 NLM | |
| 650 | 7 | |a Carbamazepine |2 NLM | |
| 650 | 7 | |a 33CM23913M |2 NLM | |
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| 700 | 1 | |a Wang, Qun |e verfasserin |4 aut | |
| 700 | 1 | |a Carrington, Blake |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Morgan |e verfasserin |4 aut | |
| 700 | 1 | |a Young, Alice C |e verfasserin |4 aut | |
| 700 | 1 | |a Birnbaum, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhao |e verfasserin |4 aut | |
| 700 | 1 | |a Ashizawa, Tetsuo |e verfasserin |4 aut | |
| 700 | 1 | |a Mullikin, James C |e verfasserin |4 aut | |
| 700 | 1 | |a Koubeissi, Mohamad Z |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Paul |e verfasserin |4 aut | |
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