Spinocerebellar ataxia type 8 is a dominantly inherited ataxia, mainly occurring in adulthood. It is caused by a CTG.CAG tract expansion in the ATXN8OS gene, an untranslated antisense transcript that partially overlaps the KLHL1 gene. We report two families, each composed of one parent and one son/daughter, segregating a small genomic deletion spanning only ATXN8OS gene and part of KLHL1. Both probands were referred for speech and articulation difficulties, and one had mild intellectual disability. The deletion was inherited from a healthy parent. Neither of the probands had signs of cerebellar dysfunction. MRI performed on two subjects of family 1 did not show brain anomalies. In contrast with the KLHL1/ATX8OS knockout mouse model, our data suggests that heterozygous deletion in KLHL1/ATX8OS is unlikely to be associated with ataxia/cerebellar involvement in humans, although it may contribute to speech/articulation problems or neuropsychiatric symptoms other than cerebellar/ataxia.

Heterozygous deletion of KLHL1/ATX8OS at the SCA8 locus is unlikely associated with cerebellar impairment in humans

MANDRILE, Giorgia;DI GREGORIO, ELEONORA;GIACHINO, Daniela Francesca;DE MERCANTI, STEFANIA FEDERICA;DE MARCHI, Mario;BRUSCO, Alfredo
2016-01-01

Abstract

Spinocerebellar ataxia type 8 is a dominantly inherited ataxia, mainly occurring in adulthood. It is caused by a CTG.CAG tract expansion in the ATXN8OS gene, an untranslated antisense transcript that partially overlaps the KLHL1 gene. We report two families, each composed of one parent and one son/daughter, segregating a small genomic deletion spanning only ATXN8OS gene and part of KLHL1. Both probands were referred for speech and articulation difficulties, and one had mild intellectual disability. The deletion was inherited from a healthy parent. Neither of the probands had signs of cerebellar dysfunction. MRI performed on two subjects of family 1 did not show brain anomalies. In contrast with the KLHL1/ATX8OS knockout mouse model, our data suggests that heterozygous deletion in KLHL1/ATX8OS is unlikely to be associated with ataxia/cerebellar involvement in humans, although it may contribute to speech/articulation problems or neuropsychiatric symptoms other than cerebellar/ataxia.
15
2
208
212
http://link.springer.com/article/10.1007%2Fs12311-015-0679-3
sca8, spinocerebellar ataxia, atxn80s, KLHL1
Mandrile, Giorgia; Di Gregorio, Eleonora; Goel, Himanshu; Giachino, Daniela; De Mercanti, Stefania; Iudicello, Marco; Rolando, Marco; Losa, Sabrina; De Marchi, Mario; Brusco, Alfredo
File in questo prodotto:
File Dimensione Formato  
sca8.pdf

Accesso aperto

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 729.5 kB
Formato Adobe PDF
729.5 kB Adobe PDF Visualizza/Apri
Mandrile et al 2016_cerebellum.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 1.51 MB
Formato Adobe PDF
1.51 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1521986
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact