Talk:Spinocerebellar ataxia type 1/GA1

GA Review

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Reviewer: Ceranthor (talk · contribs) 00:26, 19 July 2018 (UTC)

I will review this. I will try to review this in the next few days. ceranthor 00:26, 19 July 2018 (UTC)

Should be able to post comments tomorrow. ceranthor 02:07, 23 July 2018 (UTC)

Lead

• "Death typically occurs within 10 to 30 years from onset." - is it "from" or "of" onset?
  • GeneReviews source says "Interval from onset to death varies from ten to 30 years", kept preposition as is.
• Why is Ataxia capitalized in the bold text of the lead but not the article name? what's the biomedical standard?
  • made lower case
• "which, like other spinocerebellar ataxias, is characterized by dysarthria, hypermetric saccades, ataxia of gait and stance, and other neurological symptoms" - all this is linked appropriately for a lay reader, which is nice. I think it would be slightly easier to digest if this were rephrased as "is characterized by neurological symptoms including... stance" that way you imply other symptoms but introduce the neurological qualities to a lay reader
  • done
• "the children of a person with the disease have a 50% chance of inheriting it themselves and new mutations can occur in some cases" - comma before "and new mutations"
  • done
• "results in a larger than normal number of consecutive glutamine residues in the protein." - probably worth adding "amino acid" before residues for lay readers
  • done
• "This mutant protein causes degradation in types of neurons" - what does "types of" add here? why not just "in neurons..."
  • kept 'types' because only specific cell types are affected. Added ', like Purkinje neurons,' to clarify
• "This mutation can be detected before or after the onset of symptoms by genetic testing." - comes sort of abruptly; important but maybe relocate within the lead?
  • moved to first sentence of next paragraph, which seems to cover more clinical ideas like treatment.
• "SCA1 has been the subject of such high technology treatment as gene therapy and stem cell therapy. " - "high technology treatment"?
  • changed to 'research into more advanced treatment options such as...'
• "and is often linked to founders effects." - think it's founder effect
  • done
• "Ataxia, as a symptom has been known since the mid 19th century and the heterogenous group of diseases now known as spinocerebellar ataxias was the subject of extensive research in the latter part of that century" - why the comma?
  • removed comma
• "It was not until the development of techniques for analyzing molecular genetics in the 20th century that the differences between hereditary ataxias could be elucidated." - reads a little narratively for an encyclopedia; reword to cut out some of the verbiage
  • changed sentence to 'Advances in molecular genetics in the 20th century allowed distinct causes of these diseases to be identified.' Hopefully this resolves the narrative tone, let me know if it does not.
• " It was the first spinocerebellar ataxia causing gene to be localized and identified." - hyphenate "ataxia-causing"
  • done

More comments once these are addressed. ceranthor 16:48, 23 July 2018 (UTC)

I think I got them all, and am ready to move on unless I have overlooked something or introduced more issues.--Cincotta1 (talk) 23:42, 23 July 2018 (UTC)

Signs and symptoms

• "Ataxia refers to a lack of coordinated muscle movements that include gait abnormality and is the cerebellar sign that typifies all SCA types," - should probably explain what "SCA" stands for
  • expanded that instance of SCA to spinocerbellar ataxia and provided the abbr. in a parenthetical
• "where earlier onset correlates faster progression.[1]" - "correlates... with"
  • done
• "SCA 1 dysarthria may vary in severity depending on task and is often associated with more strained, strangled or harsh sounding vocalization than that of other disorders.[2]" - "depending on task" ... "the" before "task"
  • done
• "An estimated 77% of cases of progressive cerebellar disease are reported to have one or more mental health disorders and 19% exhibit cognitive disorders.[9] " - comma before "and 19%"
  • done

Genetics

• "The ATXN1 gene on chromosome 6 encodes for the ataxin 1 protein," - don't need the "for" after "encodes"
  • done
• DNA with CAG repeats are prone to forming secondary structures, including hairpin loops and R-loops which can result in mutations and mosaicism if DNA repair mechanisms fail" - need a comma before "which"
  • done

Pathophysiology

• "Normal ataxin 1 is intimately involved in a number of signaling pathways, in protein ubiquitination, RNA metabolism, in transcription regulation, protein transformation, and protein stabilization;[16][17]:149–165 it forms a transcription complex with Retinoid-related Orphan nuclear-receptor transcription factor α (RORα) following interactions with an activator, Histone acetyltransferase KAT5, sometimes referred to as TIP60,[18] and ataxin 1 is also involved in the signaling mediated by metabotropic glutamate receptor 1 (mGluR1).[19]" - too long for a topic sentence; break it up
  • Split sentence at the semi colon, prefaced new sentence with 'Among other interactions,'
• " Resonant Recognition Modeling of the ataxin 1 protein has shown possible binding sites for growth factor independent transcription repressor 1.[17]:149–16" - what does this actually mean, though?
  • It means the interaction was predicted by a computational model. The protein Gfi-1 is already known to cause degradation of Purkinje cells, so this connexion could play a role in pathogenesis. Added sentence to that effect
• "It is the extensive involvement of ataxin 1 in many different functions that make understanding the biochemical pathophysiology of its mutant form difficult to identify and understand." - no citation?
  • Cannot remember exactly which article it first came from, but this line from cite 17: "With such diversity of putative mechanisms for a single protein’s function, it is difficult to grasp a plausible hypothesis for the pathophysiology associated with the presence of long glutamine repeats" seems to fit the bill. Added another instance of that cite following the sentence
• "however rodent model studies have shown significantly later formation of nuclear inclusions of mutant proteins in cerebellum and spinal cord neurons than in cortical and hippocampal neurons which typically show only mild degeneration in SCA1 persons, suggesting a more complicated mechanism.[21]" - comma before which
  • done
• "Mutant ataxin-1 also known to alter the neural circuitry of the developing cerebellum, setting the stage for later vulnerability of Purkinje cells, suggesting the existence of non-cell autonomous toxicity.[25]" - spacing error, also I think this is a bit of a run-on
  • could not find spacing error, added missing conjunction and reworded to resolve flow issue
• "The expanded polyglutamine region results in increased affinity of the ataxin 1 AXH domain for certain transcription factors and this effect is believed to play a significant role in ataxin 1 toxicity.[28] " - comma before "and this effect"
  • done

General

• Aren't gene names italicized?
  • ital'd all instance of ATXN1 in the prose, left article titles in cites as is.
• More to come as I continue posting comments.

Mostly minor stuff left. I'll finish up tomorrow! ceranthor 03:56, 24 July 2018 (UTC)

Diagnosis and evaluation

• "Most SCAs and other ataxic disorders are clinically heterogeneous, meaning clinical signs and symptoms are similar between diseases and distinguishing between diseases with a neurologic exam alone is difficult,[1] so in symptomatic persons diagnosis of ataxia related disorders often requires a neurological exam, evaluation of neurological and family history, and molecular genetic testing. " - Again, too long for a topic sentence; split into two. I sense a recurring theme here... :)
  • I think I have a habit of being too verbose. Split at the first comma, dropped conjunction 'so'
• "Absence of a family history does not definitively exclude hereditary causes like spinocerebellar ataxia type 1 " - what does "definitively" add here?
  • removed
• "When done after the onset of symptoms, the test is said to be diagnostic" - "done" seems awkward here, replace with another word if you can
  • replaced with 'testing is administered'
• "The procedure as recommended by the European Molecular Quality Genetics Network (EMQN) sets different criteria to be met for prior to testing for each type." - grammar
  • rewrote as 'The European Molecular Quality Genetics Network (EMQN) recommends criteria for each type, which must be met before testing can begin.' not sure if this resolves the awkwording
• "Spinocerebellar ataxia type 1 was one of the first late onset diseases after Huntington's disease for which presymptomatic testing was demonstrated effective and predictive.[40]" - what does "after" imply here, that they were demonstrated after Huntington's testing? little unclear
  • added additional clause ';prior to the development of testing for SCA1, Huntington's disease was the only similar disease for which presymptomatic testing was available' dropping the more confusing wording.
• " Capillary electrophoresis (CE) is one method which has met these criteria and is recommended by the EMQN.[37][38]" - nitpicky, but prefer "that" to "which" here
  • done
• "No formal diagnostic criteria exist for most SCAs and genetic testing is the only certain diagnostic method" - comma before "and"
  • done
• " but clinical examination of signs and symptoms may be vital to distinguishing SCAs from non-genetic ataxias, other types of genetic ataxias, and for determining which genetic tests should be done first." -end of the sentence needs tweaking for grammar
  • split last point off into its own sentence 'Clinical examination can also help distinguish between SCA types to some extent, so genetic tests for certain types can be prioritized over others.'
• "Many potential differentiating symptoms have been found and methods of assessing many symptoms and their progression to guide genetic testing have been developed." - comma before and
  • done

Management

• " Overall, physical therapy for individuals with ataxia has modest evidence supporting its efficaciousness but current practice uses custom treatments without a standard decision making procedure between clinics" - comma before "but"
  • done
• "Among the earliest developed neurorehabilitation practices is Frenkel exercises, which was developed by Heinrich Frenkel in mid nineteenth century;[53]" - need a "the" before "mid nineteenth"
  • done
• "were drawn from contemporary "medical gymnastics"" - is this a direct quote? confused
  • not really a direct quote, broke the pipe link and rephrased to 'contempory physical medicine techniques, call medical gymnastics'

Prognosis

• Seems fine.

Epidemiology

• "The National Institute of Health reports SCA1 has a prevalence of approximately 1 or 2 per 100,000[59]" - "reports that"
  • done
• "Because of its late onset, often appearing after reproductive age, SCA1 exerts low selection intensity, ranking about 0.19 on the Crow's index, but intensity may vary with time within a population or family, as anticipation increases the number of CAG repeats. This means that SCA1 is unlikely to disappear from a population by natural selection alone.[58]" - is this all it means, or are you oversimplifying?
  • changed to 'One implication of this is that'
• "communities in Tamilnadu," - think it's Tamil Nadu
  • It is, done

More comments on the last two sections forthcoming. ceranthor 14:05, 24 July 2018 (UTC)

History

• "Ataxia as a symptom was first described by Duchenne de Boulogne " - worth noting that he's a French neurologist
  • done
• " extensive research into characterization, cause, and diagnostics of hereditary cerebellar ataxias " - add "the" before "characterization"
  • done
• "including Jean-Martin Charcot, Pierre Marie, Nikolaus Friedreich, Adolph Strümpell and others" - elsewhere you've used the serial comma; keep it consistent
  • done
• "Marie's ataxia was used to describe all autosomal dominant disorders marked by cerebellar degeneration and related symptoms while Friedriech's ataxia was used to describe all autosomal recessive disorders of this type." - citation?
  • removed the claim, could not find in nearby citations
• "In the depression era United States," - probably worth linking
  • piped to Great Depression in the United States

Research directions

• "several potential options for SCA1 have been under investigation over the past few years" - this last bit, "over the past few years" is vague... I'd just cut it out
  • cut
• "Because many SCAs, including SCA1, are polyglutamine diseases and operate by similar mechanisms to Huntington's disease many promising treatments for Huntington's disease are being investigated in the SCAs.[62]" - missing a comma, and "are being investigated in the SCAs" reads awkwardly
  • changed to '...being investigated for SCAs as well', again not sure if this resolves it
• "antisense oligonucleotide therapy which uses single strands of RNA complimentary to the target to prevent the target from binding to a ribosome and trigger the degradation of the target," -comma before "which"
  • done
• "This pathway crosstalks with the mGluR1 pathway which interacts with the ataxin 1 protein and proteins responsible for localization and degradation of ataxin 1," -same as above
  • done
• "One treatment option being investigated is stem cell therapy which attempts to replace dead tissue by transplanting stem cells into affected region" -same as above
  • done

References

• Earwig's tool: checks out fine.
• Any page numbers for ref 12?
  • All instances of 12 now use rp template to provide page numbers inline
• same with ref 17? and ref 70?
  • 17 already uses rp template inline
  • added another instance of cite 70 and used rp to provide ref pages for the dates in the paragraph
• Seems comprehensive
• Ref 68 has the portuguese language indicator, but not ref 67
  • added indicator to 67

And now, once these are addressed, I will be happy to pass this. ceranthor 20:47, 24 July 2018 (UTC)

@Cincotta1: Thanks for the speedy responses. Let me know once you think you've addressed everything here. ceranthor 01:15, 25 July 2018 (UTC)

I think I have gotten all the points listed above.--Cincotta1 (talk) 02:47, 25 July 2018 (UTC)

Great work! Passing now. ceranthor 03:12, 25 July 2018 (UTC)