A patient with lissencephaly, developmental delay, and infantile spasms, due to de novo heterozygous mutation of
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              <scp>KIF</scp>
              2A
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Tian, Guoling; Cristancho, Ana G.; Dubbs, Holly; Liu, Grant T.; Cowan, Nicholas J.; Goldberg, Ethan M.

doi:10.1002/mgg3.236

Cited by 19 publications

(19 citation statements)

References 12 publications

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“…Specifically, the PAFAH1B1/LIS1 and DCX genes, which are related to classical lissencephaly, appear to be associated to ISs in about 80% of affected children. A de novo heterozygous mutation of KIF2A gene has been reported in a child with lissencephaly, developmental delay, and IS [47]. Recently, a child with IS and periventricular nodular heterotopia was found to harbor an unbalanced chromosomal translocation 3p26.2-10p15.1 and a 6q22.31 duplication [48].…”

Section: Structural Brain Disordersmentioning

confidence: 99%

West syndrome: a comprehensive review

et al. 2020

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Since its first clinical description (on his son) by William James West (1793-1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) developmental arrest or regression as "West syndrome", new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances.

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Section: Structural Brain Disordersmentioning

confidence: 99%

West syndrome: a comprehensive review

et al. 2020

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“…Many members of the Kinesin superfamily have been implicated in human diseases, and some have been linked to ID (Al‐Gazali & Bakalinova, ; Aulchenko et al, ; Bouslam et al, ; Dafinger et al, ; Engle et al, ; Filges et al, ; Goizet et al, ; Hamdan et al, ; Klebe et al, ; Macedo‐Souza et al, ; Min et al, ; Novarino et al, ; Poirier et al, ; Putoux et al, ; Reid et al, ; Rivière et al, ; Saito et al, ; Schinzel & Schmid, ; Schlisio et al, ; Sener, Lee, Turgut, Akarsu, & Engle, ; Sleiman et al, ; Tian et al, ; Vasudevan et al, ; Willemsen et al, ). Surprisingly, many of these syndromes have overlapping features with our patients (Table ).…”

Section: Discussionmentioning

confidence: 99%

KIF16B is a candidate gene for a novel autosomal‐recessive intellectual disability syndrome

Alsahli

Arold

Alfares

et al. 2018

American J of Med Genetics Pt A

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Intellectual disability (ID) and global developmental delay are closely related; the latter is reserved for children under the age of 5 years as it is challenging to reliably assess clinical severity in this population. ID is a common condition, with up to 1%-3% of the population being affected and leading to a huge social and economic impact. ID is attributed to genetic abnormalities most of the time; however, the exact role of genetic involvement in ID is yet to be determined. Whole exome sequencing (WES) has gained popularity in the workup for ID, and multiple studies have been published examining the diagnostic yield in identification of the disease-causing variant (16%-55%), with the genetic involvement increasing as intelligence quotient decreases. WES has also accelerated novel disease gene discovery in this field. We identified a novel biallelic variant in the KIF16B gene (NM_024704.4:c.3611T > G) in two brothers that may be the cause of their phenotype.

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“…Kinesins, on the other hand, are a large family of proteins encoded by 44 genes scattered throughout the human genome [52,60]. Notably, mutations in the KIF5C kinesin gene have been reported in a number of patients with polymicrogyria or microcephaly, mutations in the KIF2A kinesin gene have been reported in a small group of patients with reduced cortical gyri (agyria/pachygyria) [54,61], and patients with mutations in the KIF1A kinesin gene have been found to develop pachygyria [62] and an unusual progressive form of microcephaly [63]. Noticeably, other kinesin families have been implicated in other neurodevelopmental pathologies [64–66].…”

Section: Microtubule Basics Dynamic Instability and Partnersmentioning

confidence: 99%

Tubulin mutations in neurodevelopmental disorders as a tool to decipher microtubule function

Fourel

Boscheron

2020

FEBS Letters

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Malformations of cortical development (MCDs) are a group of severe brain malformations associated with intellectual disability and refractory childhood epilepsy. Human missense heterozygous mutations in the 9 α‐tubulin and 10 β‐tubulin isoforms forming the heterodimers that assemble into microtubules (MTs) were found to cause MCDs. However, how a single mutated residue in a given tubulin isoform can perturb the entire microtubule population in a neuronal cell remains a crucial question. Here, we examined 85 MCD‐associated tubulin mutations occurring in TUBA1A, TUBB2, and TUBB3 and their location in a three‐dimensional (3D) microtubule cylinder. Mutations hitting residues exposed on the outer microtubule surface are likely to alter microtubule association with partners, while alteration of intradimer contacts may impair dimer stability and straightness. Other types of mutations are predicted to alter interdimer and lateral contacts, which are responsible for microtubule cohesion, rigidity, and dynamics. MCD‐associated tubulin mutations surprisingly fall into all categories, thus providing unexpected insights into how a single mutation may impair microtubule function and elicit dominant effects in neurons.

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A patient with lissencephaly, developmental delay, and infantile spasms, due to de novo heterozygous mutation of KIF 2A

Cited by 19 publications

References 12 publications

West syndrome: a comprehensive review

West syndrome: a comprehensive review

KIF16B is a candidate gene for a novel autosomal‐recessive intellectual disability syndrome

Tubulin mutations in neurodevelopmental disorders as a tool to decipher microtubule function

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