Pentanucleotide Repeat Insertions in RAI1 Cause Benign Adult Familial Myoclonic Epilepsy Type 8.

Autor: Yeetong P; Division of Human Genetics, Department of Botany, Faculty of Science, Chulalongkorn University, Bangkok, Thailand., Dembélé ME; Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali., Pongpanich M; Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.; Omics Sciences and Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok, Thailand., Cissé L; Service de Neurologie, Centre Hospitalier Universitaire du Point G, Bamako, Mali., Srichomthong C; Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand., Maiga AB; Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali., Dembélé K; Hôpital du District de la Commune IV, Bamako, Mali., Assawapitaksakul A; Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand., Bamba S; Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali., Yalcouyé A; Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali., Diarra S; Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali.; Pediatric Genomics Discovery Program, Department of Pediatrics, Yale University, New Haven, Connecticut, USA.; Neurogenetics Branch, NINDS, NIH, Bethesda, Maryland, USA., Mefoung SE; Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali., Rakwongkhachon S; Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand., Traoré O; Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali., Tongkobpetch S; Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand., Fischbeck KH; Neurogenetics Branch, NINDS, NIH, Bethesda, Maryland, USA., Gahl WA; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA., Guinto CO; Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali.; Service de Neurologie, Centre Hospitalier Universitaire du Point G, Bamako, Mali., Shotelersuk V; Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand., Landouré G; Faculté de Médecine et d'Odontostomatologie, USTTB, Bamako, Mali.; Service de Neurologie, Centre Hospitalier Universitaire du Point G, Bamako, Mali.
Jazyk: angličtina
Zdroj: Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2024 Jan; Vol. 39 (1), pp. 164-172. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1002/mds.29654
Abstrakt: Background: Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disorder characterized by cortical tremors and seizures. Six types of BAFME, all caused by pentanucleotide repeat expansions in different genes, have been reported. However, several other BAFME cases remain with no molecular diagnosis.
Objectives: We aim to characterize clinical features and identify the mutation causing BAFME in a large Malian family with 10 affected members.
Methods: Long-read whole genome sequencing, repeat-primed polymerase chain reaction and RNA studies were performed.
Results: We identified TTTTA repeat expansions and TTTCA repeat insertions in intron 4 of the RAI1 gene that co-segregated with disease status in this family. TTTCA repeats were absent in 200 Malian controls. In the affected individuals, we found a read with only nine TTTCA repeat units and somatic instability. The RAI1 repeat expansions cause the only BAFME type in which the disease-causing repeats are in a gene associated with a monogenic disorder in the haploinsufficiency state (ie, Smith-Magenis syndrome [SMS]). Nevertheless, none of the Malian patients exhibited symptoms related to SMS. Moreover, leukocyte RNA levels of RAI1 in six Malian BAFME patients were no different from controls.
Conclusions: These findings establish a new type of BAFME, BAFME8, in an African family and suggest that haploinsufficiency is unlikely to be the main pathomechanism of BAFME. © 2023 International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
(© 2023 International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
Databáze: MEDLINE
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