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Clinical and pathologic phenotype of a large family with heterozygous STUB1 mutation.
Mol, Merel O; van Rooij, Jeroen G J; Brusse, Esther; Verkerk, Annemieke J M H; Melhem, Shamiram; den Dunnen, Wilfred F A; Rizzu, Patrizia; Cupidi, Chiara; van Swieten, John C; Donker Kaat, Laura.
Afiliação
  • Mol MO; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
  • van Rooij JGJ; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
  • Brusse E; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
  • Verkerk AJMH; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
  • Melhem S; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
  • den Dunnen WFA; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
  • Rizzu P; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
  • Cupidi C; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
  • van Swieten JC; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
  • Donker Kaat L; Department of Neurology (M.O.M., J.G.J.v.R., E.B., S.M., J.C.v.S., L.D.K.); Department of Internal Medicine (J.G.J.v.R., A.J.M.H.V.), Erasmus Medical Center, Rotterdam; Department of Pathology and Medical Biology (W.F.A.d.D.), University Medical Centre Groningen, Groningen, the Netherlands; German C
Neurol Genet ; 6(3): e417, 2020 Jun.
Article em En | MEDLINE | ID: mdl-32337344
ABSTRACT

OBJECTIVE:

To describe the clinical and pathologic features of a novel pedigree with heterozygous STUB1 mutation causing SCA48.

METHODS:

We report a large pedigree of Dutch decent. Clinical and pathologic data were reviewed, and genetic analyses (whole-exome sequencing, whole-genome sequencing, and linkage analysis) were performed on multiple family members.

RESULTS:

Patients presented with adult-onset gait disturbance (ataxia or parkinsonism), combined with prominent cognitive decline and behavioral changes. Whole-exome sequencing identified a novel heterozygous frameshift variant c.731_732delGC (p.C244Yfs*24) in STUB1 segregating with the disease. This variant was present in a linkage peak on chromosome 16p13.3. Neuropathologic examination of 3 cases revealed a consistent pattern of ubiquitin/p62-positive neuronal inclusions in the cerebellum, neocortex, and brainstem. In addition, tau pathology was present in 1 case.

CONCLUSIONS:

This study confirms previous findings of heterozygous STUB1 mutations as the cause of SCA48 and highlights its prominent cognitive involvement, besides cerebellar ataxia and movement disorders as cardinal features. The presence of intranuclear inclusions is a pathologic hallmark of the disease. Future studies will provide more insight into its pathologic heterogeneity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Neurol Genet Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Neurol Genet Ano de publicação: 2020 Tipo de documento: Article