Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

A Faroese founder variant in TBCD causes early onset, progressive encephalopathy with a homogenous clinical course

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Genetic study of the Arctic CPT1A variant suggests that its effect on fatty acid levels is modulated by traditional Inuit diet

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Haploinsufficiency of ARHGAP42 is associated with hypertension

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. The Global State of the Genetic Counseling Profession

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  1. PET imaging of meningioma with 18F-FLT: a predictor of tumour progression

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Corticotroph aggressive pituitary tumours and carcinomas frequently harbour ATRX mutations

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

An intact and dynamic microtubule cytoskeleton is crucial for the development, differentiation, and maintenance of the mammalian cortex. Variants in a host of structural microtubulin-associated proteins have been identified to cause a wide spectrum of malformations of cortical development and alterations of microtubule dynamics have been recognized to cause or contribute to progressive neurodegenerative disorders. TBCD is one of the five tubulin-specific chaperones and is required for reversible assembly of the α-/β-tubulin heterodimer. Recently, variants in TBCD, and one other tubulin-specific chaperone, TBCE, have been identified in patients with distinct progressive encephalopathy with a seemingly broad clinical spectrum. Here, we report the clinical, neuroradiological, and neuropathological features in eight patients originating from the Faroe Islands, who presented with an early onset, progressive encephalopathy with features of primary neurodegeneration, and a homogenous clinical course. These patients were homozygous for a TBCD missense variant c.[3099C>G]; p.(Asn1033Lys), which we show has a high carrier frequency in the Faroese population (2.6%). The patients had similar age of onset as the previously reported patients (n = 24), but much shorter survival, which could be caused by either differences in supportive treatment, or alternatively, that shorter survival is intrinsic to the Faroese phenotype. We present a detailed description of the neuropathology and MR imaging characteristics of a subset of these patients, adding insight into the phenotype of TBCD-related encephalopathy. The finding of a Faroese founder variant will allow targeted genetic diagnostics in patients of Faroese descent as well as improved genetic counseling and testing of at-risk couples.

OriginalsprogEngelsk
TidsskriftEuropean journal of human genetics : EJHG
Vol/bind26
Udgave nummer10
Sider (fra-til)1512-1520
Antal sider9
ISSN1018-4813
DOI
StatusUdgivet - okt. 2018

ID: 56074796