De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy

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dc.contributor.authorJae-Ran Lee-
dc.contributor.authorS Srour-
dc.contributor.authorD Kim-
dc.contributor.authorF F Hamdan-
dc.contributor.authorSo Hee Lim-
dc.contributor.authorC Brunel-Guitton-
dc.contributor.authorJ C Decarie-
dc.contributor.authorE Rossignol-
dc.contributor.authorG A Mitchell-
dc.contributor.authorA Schreiber-
dc.contributor.authorR Moran-
dc.contributor.authorK V Haren-
dc.contributor.authorR Richardson-
dc.contributor.authorJ Nicolai-
dc.contributor.authorK M E J Oberndorff-
dc.contributor.authorJ D Wagner-
dc.contributor.authorK M Boycott-
dc.contributor.authorE Rahikkala-
dc.contributor.authorN Junna-
dc.contributor.authorH Tyynismaa-
dc.contributor.authorI Cuppen-
dc.contributor.authorN E Verbeek-
dc.contributor.authorC T R M Stumpel-
dc.contributor.authorM A Willemsen-
dc.contributor.authorS A Munnik-
dc.contributor.authorG A Rouleau-
dc.contributor.authorE Kim-
dc.contributor.authorE J Kamsteeg-
dc.contributor.authorT Kleefstra-
dc.contributor.authorJ L Michaud-
dc.date.accessioned2017-04-19T10:00:48Z-
dc.date.available2017-04-19T10:00:48Z-
dc.date.issued2015-
dc.identifier.issn1059-7794-
dc.identifier.uri10.1002/humu.22709ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/12409-
dc.description.abstractKIF1A is a neuron-specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations in KIF1A were previously described in families with spastic paraparesis or sensory and autonomic neuropathy type-2. Here, we report 11 heterozygous de novo missense mutations (p.S58L, p.T99M, p.G102D, p.V144F, p.R167C, p.A202P, p.S215R, p.R216P, p.L249Q, p.E253K, and p.R316W) in KIF1A in 14 individuals, including two monozygotic twins. Two mutations (p.T99M and p.E253K) were recurrent, each being found in unrelated cases. All these de novo mutations are located in the motor domain (MD) of KIF1A. Structural modeling revealed that they alter conserved residues that are critical for the structure and function of the MD. Transfection studies suggested that at least five of these mutations affect the transport of the MD along axons. Individuals with de novo mutations in KIF1A display a phenotype characterized by cognitive impairment and variable presence of cerebellar atrophy, spastic paraparesis, optic nerve atrophy, peripheral neuropathy, and epilepsy. Our findings thus indicate that de novo missense mutations in the MD of KIF1A cause a phenotype that overlaps with, while being more severe, than that associated with recessive mutations in the same gene.-
dc.publisherWiley-
dc.titleDe novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy-
dc.title.alternativeDe novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy-
dc.typeArticle-
dc.citation.titleHuman Mutation-
dc.citation.number1-
dc.citation.endPage78-
dc.citation.startPage69-
dc.citation.volume36-
dc.contributor.affiliatedAuthorJae-Ran Lee-
dc.contributor.affiliatedAuthorSo Hee Lim-
dc.contributor.alternativeName이재란-
dc.contributor.alternativeNameSrour-
dc.contributor.alternativeName김도연-
dc.contributor.alternativeNameHamdan-
dc.contributor.alternativeName임소희-
dc.contributor.alternativeNameBrunel-Guitton-
dc.contributor.alternativeNameDecarie-
dc.contributor.alternativeNameRossignol-
dc.contributor.alternativeNameMitchell-
dc.contributor.alternativeNameSchreiber-
dc.contributor.alternativeNameMoran-
dc.contributor.alternativeNameHaren-
dc.contributor.alternativeNameRichardson-
dc.contributor.alternativeNameNicolai-
dc.contributor.alternativeNameOberndorff-
dc.contributor.alternativeNameWagner-
dc.contributor.alternativeNameBoycott-
dc.contributor.alternativeNameRahikkala-
dc.contributor.alternativeNameJunna-
dc.contributor.alternativeNameTyynismaa-
dc.contributor.alternativeNameCuppen-
dc.contributor.alternativeNameVerbeek-
dc.contributor.alternativeNameStumpel-
dc.contributor.alternativeNameWillemsen-
dc.contributor.alternativeNameMunnik-
dc.contributor.alternativeNameRouleau-
dc.contributor.alternativeName김은준-
dc.contributor.alternativeNameKamsteeg-
dc.contributor.alternativeNameKleefstra-
dc.contributor.alternativeNameMichaud-
dc.identifier.bibliographicCitationHuman Mutation, vol. 36, no. 1, pp. 69-78-
dc.identifier.doi10.1002/humu.22709-
dc.subject.keywordAxonal neuropathy-
dc.subject.keywordDe novo mutations-
dc.subject.keywordIntellectual disability-
dc.subject.keywordKIF1A-
dc.subject.keywordSpastic paraparesis-
dc.subject.localAxonal neuropathy-
dc.subject.localDe novo mutations-
dc.subject.localIntellectual disability-
dc.subject.localintellectual disability-
dc.subject.localKIF1A-
dc.subject.localSpastic paraparesis-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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