Evidence for a common founder effect amongst South African and Zambian individuals with Spinocerebellar ataxia type 7

Smith, Danielle C.; Atadzhanov, Masharip; Mwaba, Mwila Hilton; Greenberg, L J

doi:10.1016/j.jns.2015.04.053

Cited by 15 publications

(11 citation statements)

References 23 publications

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“…16 SCA7 is considered to be rare, although founder effects have been reported in South Africa, Scandinavia, and Mexico. 15,17 The pathology of this disorder include atrophy of the spinocerebellar pathways, pyramidal tracts, and motor nuclei in the brainstem and spinal cord, a cone-rod dystrophy of the retina, and ataxin-7 immunoreactive neuronal intranuclear inclusion. 18 The spectrum of clinical severity in SCA7 ranges from infantile-onset with early death to elderly presentations of slowly progressive isolated ataxia depending on the number of CAG repetitions.…”

Section: Discussionmentioning

confidence: 99%

Ophthalmic features of spinocerebellar ataxia type 7

Campos‐Romo

Graue-Hernandez

Pedro-Aguilar

et al. 2017

Eye

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PurposeTo analyze the relation between ophthalmologic and motor changes in spinocerebellar ataxia type 7 (SCA7).Patients and methodsThis was a case series study. Sixteen SCA7 patients underwent a comprehensive ophthalmic examination, including ocular extrinsic motility testing, color vision test, and optical coherence tomography of the optic nerve and macula. Changes in the corneal endothelium, electroretinographic patterns, and a complete neurologic evaluation using the Scale for the Assessment and Rating of Ataxia (SARA) were evaluated. Correlations of endothelial cell density (ECD) with number of CAG repetitions and the SARA scores were estimated.ResultsAll patients showed various degrees of visual impairment mainly due to macular deterioration. Notably, they also presented decreased ECD. Pairwise correlations of ECD with number of CAG repeats and severity of motor symptoms quantified with the SARA scores were inverse (r=-0.46, P=0.083 and r=-0.64, P=0.009, respectively). Further analyses indicated an average ECD decrease of 48 cells/mm (P=0.006) per unit of change on the number of CAG repeats, and of 75 cells/mm (P=0.001) per unit of change on the SARA scores.ConclusionsThe results agree with previous ophthalmological findings regarding the widespread effect of SCA7 mutation on the patient's visual system. However, the results also show a significant negative correlation of decreased ECD with both CAG repetitions and SARA scores. This suggests that motor systems could degenerate in parallel with visual systems, although more research is needed to determine whether the degeneration is caused by the same mechanisms.

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Section: Discussionmentioning

confidence: 99%

Ophthalmic features of spinocerebellar ataxia type 7

Campos‐Romo

Graue-Hernandez

Pedro-Aguilar

et al. 2017

Eye

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“…A haplotype study in 13 families from the indigenous Black African population of SA provided evidence for a SCA7 founder effect [ 11 , 12 ]. Importantly, haplotype studies based on Families 1 and 4 have confirmed that this SA SCA7 haplotype extends to northern Namibia and Zambia [ 35 ]. Considering the geographical distribution of these families, it’s feasible to hypothesize that the South African SCA7 founder effect extends to additional neighbouring countries such as Botswana and Zimbabwe.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic analysis of spinocerebellar ataxia type 7 (SCA7) in Zambian families

et al. 2017

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BackgroundTo date, 43 types of Spinocerebellar Ataxias (SCAs) have been identified. A subset of the SCAs are caused by the pathogenic expansion of a CAG repeat tract within the corresponding gene. Ethnic and geographic differences are evident in the prevalence of the autosomal dominant SCAs. Few descriptions of the clinical phenotype and molecular genetics of the SCAs are available from the African continent. Established studies mostly concern the South African populations, where there is a high frequency of SCA1, SCA2 and SCA7. The SCA7 mutation in South Africa (SA) has been found almost exclusively in families of indigenous Black African ethnic origin.ObjectiveTo present the results of the first clinical description of seven Zambian families presenting with autosomal dominant SCA, as well as the downstream molecular genetic analysis of a subset of these families.MethodsThe study was undertaken at the University Teaching Hospital in Lusaka, Zambia. Ataxia was quantified with the Brief Ataxia Rating Scale derived from the modified international ataxia rating scale. Molecular genetic testing for 5 types of SCA (SCA1, SCA2, SCA3, SCA6 and SCA7) was performed at the National Health Laboratory Service at Groote Schuur Hospital and the Division of Human Genetics, University of Cape Town, SA. The clinical and radiological features were evaluated in seven families with autosomal dominant cerebellar ataxia. Molecular genetic analysis was completed on individuals representing three of the seven families.ResultsAll affected families were ethnic Zambians from various tribes, originating from three different regions of the country (Eastern, Western and Central province). Thirty-four individuals from four families had phenotypic features of SCA7. SCA7 was confirmed by molecular testing in 10 individuals from 3 of these families. The age of onset of the disease varied from 12 to 59 years. The most prominent phenotypic features in these families were gait and limb ataxia, dysarthria, visual loss, ptosis, ophthalmoparesis/ophthalmoplegia, pyramidal tract signs, and dementia. Affected members of the SCA7 families had progressive macular degeneration and cerebellar atrophy. All families displayed marked anticipation of age at onset and rate of symptom progression. The pathogenic SCA7 CAG repeat ranges varied from 47 to 56 repeats. Three additional families were found to have clinical phenotypes associated with autosomal dominant SCA, however, DNA was not available for molecular confirmation. The age of onset of the disease in these families varied from 19 to 53 years. The most common clinical picture in these families included a combination of cerebellar symptoms with slow saccadic eye movements, peripheral neuropathy, dementia and tremor.ConclusionSCA is prevalent in ethnic Zambian families. The SCA7 families in this report had similar clinical presentations to families described in other African countries. In all families, the disease had an autosomal dominant pattern of inheritance across multiple generations. All families disp...

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“…The existing reports of neurogenetic research in Africa have shown that the genetic underpinnings of certain neurological phenotypes segregate almost exclusively in African populations. Examples include Huntington disease-like type 2 ( 31 , 32 ), spinocerebellar ataxia type 7 (SCA7) ( 33 , 34 ) and RYR1 -related centronuclear myopathy ( 35 ). However, published epilepsy research emanating from the continent focuses on the disease epidemiology, etiology, and management ( 3 , 8 , 36 – 40 ), and little is known about the genetic causes in African patients.…”

Section: Epilepsy Research In Africamentioning

confidence: 99%

Clinical Application of Epilepsy Genetics in Africa: Is Now the Time?

et al. 2018

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Over 80% of people with epilepsy live in low- to middle-income countries where epilepsy is often undiagnosed and untreated due to limited resources and poor infrastructure. In Africa, the burden of epilepsy is exacerbated by increased risk factors such as central nervous system infections, perinatal insults, and traumatic brain injury. Despite the high incidence of these etiologies, the cause of epilepsy in over 60% of African children is unknown, suggesting a possible genetic origin. Large-scale genetic and genomic research in Europe and North America has revealed new genes and variants underlying disease in a range of epilepsy phenotypes. The relevance of this knowledge to patient care is especially evident among infants with early-onset epilepsies, where early genetic testing can confirm the diagnosis and direct treatment, potentially improving prognosis and quality of life. In Africa, however, genetic epilepsies are among the most under-investigated neurological disorders, and little knowledge currently exists on the genetics of epilepsy among African patients. The increased diversity on the continent may yield unique, important epilepsy-associated genotypes, currently absent from the North American or European diagnostic testing protocols. In this review, we propose that there is strong justification for developing the capacity to offer genetic testing for children with epilepsy in Africa, informed mostly by the existing counseling and interventional needs. Initial simple protocols involving well-recognized epilepsy genes will not only help patients but will give rise to further clinically relevant research, thus increasing knowledge and capacity.

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Evidence for a common founder effect amongst South African and Zambian individuals with Spinocerebellar ataxia type 7

Cited by 15 publications

References 23 publications

Ophthalmic features of spinocerebellar ataxia type 7

Ophthalmic features of spinocerebellar ataxia type 7

Clinical and genetic analysis of spinocerebellar ataxia type 7 (SCA7) in Zambian families

Clinical Application of Epilepsy Genetics in Africa: Is Now the Time?

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