Deciphering the natural history of SCA7 in children

Bah, M. G.; Cazeneuve, Cécile; Mochel, Fanny; Devos, David; Suppiej, Agnese; Roubertie, Agathe; Meunier, Isabelle; Gitiaux, Cyril; Curie, Aurore; Klapczynski, Frédéric; Allani-Essid, N.; Carneiro, Maryline; Minkelen, Rick van; Kievit, Anneke J.A.; Fluss, Joël Victor; Leheup, B.; Ratbi, L.; Héron, Delphine; Gras, Domitille; Cao, Jérémy Do; Pichard, Samia; Strubi‐Villaume, I.; Audo, Isabelle; Lesca, Gaëtan; Charles, Perrine; Dubois, Fanny; Comet‐Didierjean, P.; Capri, Yline; Barondiot, C.; Barathon, M.; Ewenczyk, Claire; Dürr, Alexandra; Mignot, Cyril

doi:10.1111/ene.14405

Cited by 15 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SCA7 is another polyQ SCA in which there are clear records of relevant instabilities. Five de novo SCA7 cases [64][65][66] and 28 SCA7 cases with onset at childhood, six of them inherited from asymptomatic transmitting parents 67 have been reported. SCA7 also resembles SCA2 in the length of pathogenic repeats.…”

Section: Discussionmentioning

confidence: 99%

Spinocerebellar ataxia type 2 from an evolutionary perspective: Systematic review and meta‐analysis

et al. 2021

View full text Add to dashboard Cite

Dominant diseases due to expanded CAG repeat tracts, such as spinocerebellar ataxia type 2 (SCA2), are prone to anticipation and worsening of clinical picture in subsequent generations. There is insufficient data about selective forces acting on the maintenance of these diseases in populations. We made a systematic review and meta‐analysis on the effect of the CAG length over age at onset, instability of transmissions, anticipation, de novo or sporadic cases, fitness, segregation of alleles, and ancestral haplotypes. The correlation between CAG expanded and age at onset was r2 = 0.577, and transmission of the mutant allele was associated with an increase of 2.42 CAG repeats in the next generation and an anticipation of 14.62 years per generation, on average. One de novo and 18 sporadic cases were detected. Affected SCA2 individuals seem to have more children than controls. The expanded allele was less segregated than the 22‐repeat allele in children of SCA2 subjects. Several ancestral SCA2 haplotypes were published. Data suggest that SCA2 lineages may tend to disappear eventually, due to strong anticipation phenomena. Whether or not the novel cases come from common haplotypes associated with a predisposition to further expansions is a question that needs to be addressed by future studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Spinocerebellar ataxia type 2 from an evolutionary perspective: Systematic review and meta‐analysis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Although the range of normal and pathogenic repeat tract lengths differs from one polyglutamine disease to another, larger expansions are more unstable, cause earlier onset, and affect far more tissues than smaller expansions (Orr & Zoghbi, 2007). For example, adult-onset SCA7 presents as ataxia, but infantile SCA7 affects the entire nervous system, the heart, and the kidneys, and leads to death by two years of age (Bah et al , 2020). Another example is Huntington’s disease (HD), where the juvenile form frequently lacks the classic chorea yet produces seizures, which are not a feature of the adult-onset disease; brain morphometry is also quite different in adult- and juvenile-onset cases (Tereshchenko et al , 2019).…”

Section: Discussionmentioning

confidence: 99%

Dosage sensitivity in Pumilio1-related phenotypes reflects distinct disease mechanisms

Botta

Chemiakine

et al. 2021

Preprint

View full text Add to dashboard Cite

The RNA-binding protein (RBP) Pumilio1 (PUM1) is associated with two distinct diseases: a late-onset ataxia and a neurodevelopmental syndrome. The ataxia patients retain 75% of normal PUM1 levels, the syndromic patients ~50%, but this seems inadequate to explain the difference in phenotypes. We hypothesized that mild disease results from dysregulation of PUM1 targets, whereas severe disease involves disruption of PUM1 complexes and deregulation of shared targets. We therefore developed a PUM1 interactome for the murine brain and found that PUM1 shares targets with several RBP interactors (PUM2, FMRP, AGO2, and RBFOX3). PUM1 haploinsufficiency destabilizes these RBPs to varying degrees by brain region and sex, and alters expression of their shared targets, but the milder disease-causing mutation affects only PUM1-specific targets. These data indicate that dosage-sensitive proteins can produce different phenotypes by different mechanisms, and that there may be more intimate cooperation among RBPs than expected.

show abstract

“…SCA7 is caused by a CAG triplet expansion in ATXN7 at the 3p14.1 locus. The normal allele contains 7 to 17 repeats, and up to 35 repeats in asymptomatic patients, whereas symptomatic patients presents 36 or more CAG triplets [ 138 – 141 ]. SCA7 has been described in several North African families, with extended CAG repeats [ 139 , 142 – 144 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic spectrums of 413 North African families with inherited retinal dystrophies and optic neuropathies

Bouzidi

Charoute

Charif

et al. 2022

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background Inherited retinal dystrophies (IRD) and optic neuropathies (ION) are the two major causes world-wide of early visual impairment, frequently leading to legal blindness. These two groups of pathologies are highly heterogeneous and require combined clinical and molecular diagnoses to be securely identified. Exact epidemiological studies are lacking in North Africa, and genetic studies of IRD and ION individuals are often limited to case reports or to some families that migrated to the rest of the world. In order to improve the knowledge of their clinical and genetic spectrums in North Africa, we reviewed published data, to illustrate the most prevalent pathologies, genes and mutations encountered in this geographical region, extending from Morocco to Egypt, comprising 200 million inhabitants. Main body We compiled data from 413 families with IRD or ION together with their available molecular diagnosis. The proportion of IRD represents 82.8% of index cases, while ION accounted for 17.8%. Non-syndromic IRD were more frequent than syndromic ones, with photoreceptor alterations being the main cause of non-syndromic IRD, represented by retinitis pigmentosa, Leber congenital amaurosis, and cone-rod dystrophies, while ciliopathies constitute the major part of syndromic-IRD, in which the Usher and Bardet Biedl syndromes occupy 41.2% and 31.1%, respectively. We identified 71 ION families, 84.5% with a syndromic presentation, while surprisingly, non-syndromic ION are scarcely reported, with only 11 families with autosomal recessive optic atrophies related to OPA7 and OPA10 variants, or with the mitochondrial related Leber ION. Overall, consanguinity is a major cause of these diseases within North African countries, as 76.1% of IRD and 78.8% of ION investigated families were consanguineous, explaining the high rate of autosomal recessive inheritance pattern compared to the dominant one. In addition, we identified many founder mutations in small endogamous communities. Short conclusion As both IRD and ION diseases constitute a real public health burden, their under-diagnosis in North Africa due to the absence of physicians trained to the identification of inherited ophthalmologic presentations, together with the scarcity of tools for the molecular diagnosis represent major political, economic and health challenges for the future, to first establish accurate clinical diagnoses and then treat patients with the emergent therapies.

show abstract

Deciphering the natural history of SCA7 in children

Cited by 15 publications

References 32 publications

Spinocerebellar ataxia type 2 from an evolutionary perspective: Systematic review and meta‐analysis

Spinocerebellar ataxia type 2 from an evolutionary perspective: Systematic review and meta‐analysis

Dosage sensitivity in Pumilio1-related phenotypes reflects distinct disease mechanisms

Clinical and genetic spectrums of 413 North African families with inherited retinal dystrophies and optic neuropathies

Contact Info

Product

Resources

About