Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti-Boltshauser syndrome)

Eugenio Maria Mercuri, Enrico Silvio Bertini, Alessia Micalizzi, Andrea Poretti, Marta Romani, Monia Ginevrino, Tommaso Mazza, Chiara Aiello, Ginevra Zanni, Bastian Baumgartner, Renato Borgatti, Knut Brockmann, Ana Camacho, Gaetano Cantalupo, Martin Haeusler, Christiane Hikel, Andrea Klein, Giorgia Mandrile, Dietz Rating, Romina RomanielloFilippo Maria Santorelli, Mareike Schimmel, Luigina Spaccini, Serap Teber, Arpad Von Moers, Sarah Wente, Andreas Ziegler, Andrea Zonta, Enrico Bertini, Eugen Boltshauser, Enza Maria Valente

Risultato della ricerca: Contributo in rivistaArticolo in rivista

18 Citazioni (Scopus)

Abstract

Cerebellar dysplasia with cysts and abnormal shape of the fourth ventricle, in the absence of significant supratentorial anomalies and of muscular involvement, defines recessively inherited Poretti-Boltshauser syndrome (PBS). Clinical features comprise non-progressive cerebellar ataxia, intellectual disability of variable degree, language impairment, ocular motor apraxia and frequent occurrence of myopia or retinopathy. Recently, loss-of-function variants in the LAMA1 gene were identified in six probands with PBS. Here we report the detailed clinical, neuroimaging and genetic characterization of 18 PBS patients from 15 unrelated families. Biallelic LAMA1 variants were identified in 14 families (93%). The only non-mutated proband presented atypical clinical and neuroimaging features, challenging the diagnosis of PBS. Sixteen distinct variants were identified, which were all novel. In particular, the frameshift variant c.[2935delA] recurred in six unrelated families on a shared haplotype, suggesting a founder effect. No LAMA1 variants could be detected in 27 probands with different cerebellar dysplasias or non-progressive cerebellar ataxia, confirming the strong correlate between LAMA1 variants and PBS.
Lingua originaleEnglish
pagine (da-a)1262-1267
Numero di pagine6
RivistaEuropean Journal of Human Genetics
Volume24
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Genetics
  • Genetics (clinical)

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