TY - JOUR
T1 - Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti-Boltshauser syndrome)
AU - Micalizzi, Alessia
AU - Poretti, Andrea
AU - Romani, Marta
AU - Ginevrino, Monia
AU - Mazza, Tommaso
AU - Aiello, Chiara
AU - Zanni, Ginevra
AU - Baumgartner, Bastian
AU - Borgatti, Renato
AU - Brockmann, Knut
AU - Camacho, Ana
AU - Cantalupo, Gaetano
AU - Haeusler, Martin
AU - Hikel, Christiane
AU - Klein, Andrea
AU - Mandrile, Giorgia
AU - Mercuri, Eugenio
AU - Rating, Dietz
AU - Romaniello, Romina
AU - Santorelli, Filippo Maria
AU - Schimmel, Mareike
AU - Spaccini, Luigina
AU - Teber, Serap
AU - Von Moers, Arpad
AU - Wente, Sarah
AU - Ziegler, Andreas
AU - Zonta, Andrea
AU - Bertini, Enrico
AU - Boltshauser, Eugen
AU - Valente, Enza Maria
N1 - Funding Information:
This work was supported by the European Research Council (ERC Starting Grant 260888).
Publisher Copyright:
© 2016 Macmillan Publishers Limited, part of Springer Nature.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
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U2 - 10.1038/ejhg.2016.19
DO - 10.1038/ejhg.2016.19
M3 - Article
C2 - 26932191
AN - SCOPUS:84959516616
SN - 1018-4813
VL - 24
SP - 1262
EP - 1267
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 9
ER -