Explore the vast range of titles available.

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. Familial cortical myoclonic tremor (FAME) has so far been mapped to regions on chromosome 2, 3, 5 and 8 and pentameric repeat expansions in SAMD12 were identified as cause of FAME1. Here, Corbett et al . identify ATTTT/ATTTC repeat expansions in intron 1 of STARD7 in individuals with FAME2.”

G2019S in LRRK2 is the most common mutation associated with Parkinson’s disease (PD). Highest frequencies are in North African Arabic (30–41%) and Ashkenazi Jewish (6–30%) populations, mostly due to founder effects. Here, we investigated the frequency of G2019S in 647 unrelated South African PD patients from different ancestral origins. It was found in only 1.2% (8/647) of patients. Notably, none of the 91 individuals of African ancestry had G2019S. It was present in 1.9% (3/154) and 1% (5/493) of early- and late-onset cases, respectively. The frequency of G2019S exhibits ethnic-specific differences and warrants further study in sub-Saharan African populations.

Myoclonus is a complex disorder of rapid repetitive muscle jerks that can occur in proximal or distal appendicular or axial muscles. It can be of cortical, subcortical or spinal cord origin; part of progressive and severely disabling epilepsy syndromes, basal ganglia conditions, and physiological or even functional (psychogenic).A systematic review of the literature shows the knowledge gap of the genetic causes of myoclonus in South Africa with 25 identified publications from Africa of which eleven were from South Africa. Publications varied from case studies to case series and included four publications with cortical myoclonic tremor (CMT) and two with North Sea Progressive Myoclonic Epilepsy, two with subcortical myoclonus and case studies with rare cases of individuals with myoclonic disorders.In this publication the study of myoclonus in three different settings is presented. In the first: cortical myoclonic tremor (CMT), a rapid distal form of myoclonus, resembling tremor, with neurophysiological evidence of cortical origin. The study researched a South African family with Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE). The first part of this study showed the median onset of cortical tremor 16 was and that of epilepsy was 42 years; patients were stable with long term follow up after 30 years without evidence of progressive ataxia or cognitive impairment. The second part of the study presents the discovery of the genetic mutation causing this condition: a pentanucleotide repeat expansion in the intronic region of the STARD7 gene. This mutation was also found in families with FCMTE2 with a similar phenotype and followed on work showing pentanucleotide repeat expansion mutations in other forms of FCMTE in different genetic locations.The second setting proved a new mutation, a premature stop mutation p.L275X, in the epsilon-sarcoglycan gene causing subcortical origin, Myoclonus Dystonia Syndrome (MDS) in a three generation South African family with mild phenotype differences in the clinical presentation: myoclonus and dystonia in the same appendicular body part as well as truncal. Two of the affected individuals studied underwent Deep Brain Stimulation surgery of the Globus Pallidum with significant sustained improvement in the motor and non-motor features of MDS recorded and confirmed by a blinded rater.In the third setting, two patients with sporadic Paroxysmal Non-kinesigenic dyskinesia (PNKD) with the complex phenomenology of episodic dystonia, myoclonus and chorea of South African origin is presented. Both patients underwent successful DBS of the pallidum with long-term outcomes presented. Although these two individuals were not tested for the known myofibrillogenesis regulator-1 (MR-1) mutation they represent two cases of this rare disorder from South African setting and prove the successful use of DBS treatment.

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. L'épilepsie myoclonique familiale de l'adulte (FAME) se caractérise par un tremblement myoclonique cortical, généralement observé dès la deuxième décennie de vie, et par des crises myocloniques manifestes ou tonico-cloniques généralisées. Quatre loci indépendants ont été impliqués dans la FAME sur les chromosomes (chr) 2, 3, 5 et 8. Grâce au séquençage du génome entier et à la PCR avec amorce répétée, nous démontrons que la FAME liée à chr2 (FAME2) est causée par une expansion d'un pentamère ATTTC dans le premier intron de STARD7 . Les expansions ATTTC se ségréguent chez 158/158 individus typiquement atteints de FAME, issus de 22 généalogies, dont 16 familles précédemment identifiées et recrutées dans le monde entier. Le séquençage de l'ARN des fibroblastes dérivés des patients ne montre aucune accumulation des séquences répétées AUUUU ou AUUUC, et l'expression du gène STARD7 n'est pas affectée. Ces données, combinées à d’autres gènes portant des mutations similaires qui ont été impliquées dans FAME, suggèrent que les expansions ATTTC peuvent être à l’origine de ce trouble, quel que soit le locus génomique impliqué.