Infantile nystagmus and late onset ataxia associated with a CACNA1A mutation in the intracellular loop between s4 and s5 of domain 3

Self, James; Mercer, Catherine; Boon, Elles M. J.; Murugavel, M; Shawkat, Fatima; Hammans, Simon; Hodgkins, P R; Griffiths, Helen; Lotery, Andrew

doi:10.1038/eye.2008.389

Cited by 14 publications

(4 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although FRMD7 mutations are the only known genetic cause of IINS, many disorders are known to masquerade as IINS in children. These conditions are often missed due to the difficulty in identifying associated phenotypes in children (such as hypomorphic albinism 2 ) or a delay in the onset of additional clinical features (such as spino-cerebellar ataxia type 6 3 ).…”

Section: Introductionmentioning

confidence: 99%

A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping

O’Gorman

Norman

Michaels

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Nystagmus is a disorder of uncontrolled eye movement and can occur as an isolated trait (idiopathic INS, IINS) or as part of multisystem disorders such as albinism, significant visual disorders or neurological disease. Eighty-one unrelated patients with nystagmus underwent routine ocular phenotyping using commonly available phenotyping methods and were grouped into four sub-cohorts according to the level of phenotyping information gained and their findings. DNA was extracted and sequenced using a broad utility next generation sequencing (NGS) gene panel. A clinical subpanel of genes for nystagmus/albinism was utilised and likely causal variants were prioritised according to methods currently employed by clinical diagnostic laboratories. We determine the likely underlying genetic cause for 43.2% of participants with similar yields regardless of prior phenotyping. This study demonstrates that a diagnostic workflow combining basic ocular phenotyping and a clinically available targeted NGS panel, can provide a high diagnostic yield for patients with infantile nystagmus, enabling access to disease specific management at a young age and reducing the need for multiple costly, often invasive tests. By describing diagnostic yield for groups of patients with incomplete phenotyping data, it also permits the subsequent design of ‘real-world’ diagnostic workflows and illustrates the changing role of genetic testing in modern diagnostic workflows for heterogeneous ophthalmic disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping

O’Gorman

Norman

Michaels

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…We agree with the authors comment that INS is characterised by a few key features which can help differentiate it from other causes of nystagmus in children [5]. However, those stated are not the key features, which aid the clinician and many features are missing.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 36%

Is This Actually CIN?

Self

Salman

Hedley-Lewis

2015

Pediatric Neurology

View full text Add to dashboard Cite

“…This increase in genetic diagnoses has identified that a number of conditions known to cause nystagmus in some patients can indeed present as apparently isolated nystagmus and that ‘hypomorphic phenotypes’ are quite common. 5 , 7 , 8 This has had important implications for investigation pathways and management of patients with genetic forms of nystagmus and has highlighted the necessity of a structured and methodical investigation pathway which may require access to equipment and expertise which is not currently available in all clinical centres. An example of a modern diagnostic workflow for children with nystagmus illustrates that genetic panel testing is now key to an efficient and effective clinical service ( Figure 1 ).…”

Section: Introduction To Nystagmus Geneticsmentioning

confidence: 99%

“…Despite significant advances in diagnostics in some centres, 7 – 9 in the majority of cases worldwide, the underlying cause of nystagmus, even for likely genetic cases, is not identified. This has meant that the development and evaluation of novel therapeutics for conditions which feature nystagmus have often been hampered by small patient numbers or meant that therapeutics have been evaluated on patients without a genetic diagnosis and therefore have been targeted at widely varying underlying aetiologies rather than homogeneous patient groups.…”

Section: Introduction To Nystagmus Geneticsmentioning

confidence: 99%

Novel therapeutics in nystagmus: what has the genetics taught us so far?

Self

Lee

2021

Therapeutic Advances in Rare Disease

View full text Add to dashboard Cite

Nystagmus is a disorder characterised by uncontrolled, repetitive, to-and-fro movement of the eyes. It can occur as a seemingly isolated disorder but is most commonly the first, or most obvious, feature in a host of ophthalmic and systemic disorders. The number of underlying causes is vast, and recent improvements in the provision of genetic testing have shown that many conditions can include nystagmus as a feature, but that phenotypes overlap significantly. Therefore, an increase in the understanding of the genetic causes of nystagmus has shown that successful novel therapeutics for ‘nystagmus’ can target either specific underlying disorders and mechanisms (aiming to treat the underlying condition as a whole), or a final common pathway (aiming to treat the nystagmus directly). Plain language summary Novel treatments for a disorder of eye movement (nystagmus): what has the genetics taught us so far? Nystagmus is a disorder of eye movement characterised by uncontrolled, to-and-fro movements. It can occur as an isolated disorder, in conditions affecting other parts of the eye, in conditions affecting multiple other parts of the body or secondary to neurological diseases (brain diseases). In recent years, advances in genetic testing methods and increase in genetic testing in healthcare systems have provided a greater understanding of the underlying causes of nystagmus. They have highlighted the bewildering number of genetic causes that can result in what looks like a very similar eye movement disorder. In recent years, new classes of drugs have been developed for some of the causes of nystagmus, and some new drugs have been developed for other conditions which have the potential to work in certain types of nystagmus. For these reasons, genetics has taught us that identifying new possible treatments for nystagmus can either be dependent on identifying the underlying genetic cause and aiming to treat that, or aiming to treat the nystagmus per se by targeting a final common pathway. A toolkit based on specific treatments for specific conditions is more to have meaningful impact on ‘nystagmus’ than pursuing a panacea based on a ‘one size fits all’ approach.

show abstract

Infantile nystagmus and late onset ataxia associated with a CACNA1A mutation in the intracellular loop between s4 and s5 of domain 3

Cited by 14 publications

References 12 publications

A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping

A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping

Is This Actually CIN?

Novel therapeutics in nystagmus: what has the genetics taught us so far?

Contact Info

Product

Resources

About