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13.04.2019 | Original Article

Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556

verfasst von: Edmund S. Cauley, Ahlam Hamed, Inaam N. Mohamed, Maha Elseed, Samantha Martinez, Ashraf Yahia, Fatima Abozar, Rayan Abubakr, Mahmoud Koko, Liena Elsayed, Xianhua Piao, Mustafa A. Salih, M. Chiara Manzini

Erschienen in: Neurogenetics | Ausgabe 2/2019

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Abstract

Genetic mutations associated with brain malformations can lead to a spectrum of severity and it is often difficult to determine whether there are additional pathogenic variants contributing to the phenotype. Here, we present a family affected by a severe brain malformation including bilateral polymicrogyria, hydrocephalus, patchy white matter signal changes, and cerebellar and pontine hypoplasia with elongated cerebellar peduncles leading to the molar tooth sign. While the malformation is reminiscent of bilateral frontoparietal polymicrogyria (BFPP), the phenotype is more severe than previously reported and also includes features of Joubert syndrome (JBTS). Via exome sequencing, we identified homozygous truncating mutations in both ADGRG1/GPR56 and KIAA0556, which are known to cause BFPP and mild brain-specific JBTS, respectively. This study shows how two independent mutations can interact leading to complex brain malformations.

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Titel: Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556
verfasst von: Edmund S. Cauley
Ahlam Hamed
Inaam N. Mohamed
Maha Elseed
Samantha Martinez
Ashraf Yahia
Fatima Abozar
Rayan Abubakr
Mahmoud Koko
Liena Elsayed
Xianhua Piao
Mustafa A. Salih
M. Chiara Manzini
Publikationsdatum: 13.04.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Neurogenetics / Ausgabe 2/2019
Print ISSN: 1364-6745
Elektronische ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-019-00577-2

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Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556

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