Dataset Information

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

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.

SUBMITTER: Micalizzi A

PROVIDER: S-EPMC4913877 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Micalizzi Alessia A Poretti Andrea A Romani Marta M Ginevrino Monia M Mazza Tommaso T Aiello Chiara C Zanni Ginevra G Baumgartner Bastian B Borgatti Renato R Brockmann Knut K Camacho Ana A Cantalupo Gaetano G Haeusler Martin M Hikel Christiane C Klein Andrea A Mandrile Giorgia G Mercuri Eugenio E Rating Dietz D Romaniello Romina R Santorelli Filippo Maria FM Schimmel Mareike M Spaccini Luigina L Teber Serap S von Moers Arpad A Wente Sarah S Ziegler Andreas A Zonta Andrea A Bertini Enrico E Boltshauser Eugen E Valente Enza Maria EM

European journal of human genetics : EJHG 20160302 9

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 ...[more]

PMID: 26932191

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Dataset Information

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

Publications

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

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