PRUNE1 Deficiency: Expanding the Clinical and Genetic Spectrum
| Autor: | Friedrich G. Wörmann, Jan Senderek, Bader Alhaddad, Reka Kovacs-Nagy, Nicole I. Wolf, Uwe Ahting, Tilman Polster, Johannes Zschocke, Peter Freisinger, Katharina Vill, Michael Hubmann, Tobias B. Haack, Birgit Krabichler, René G. Feichtinger, Thomas Meitinger, Holger Prokisch, Johannes A. Mayr, Christine Makowski, Tim M. Strom, Agnès Rötig, Robert Kopajtich, Isabelle Desguerre, Charu Deshpande, Anna Schossig, Felix Distelmaier, Matthias C. Braunisch, Wolfgang Müller-Felber, Heinz Jungbluth, Johannes Koch |
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| Přispěvatelé: | Pediatric surgery, Amsterdam Neuroscience - Cellular & Molecular Mechanisms |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug Resistant Epilepsy Pediatrics medicine.medical_specialty Microcephaly Genetic Linkage Developmental Disabilities Mutation Missense Disease medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Exome Sequencing medicine Humans Missense mutation Global developmental delay Child Exome sequencing Mutation business.industry Brain General Medicine medicine.disease Dysphagia Phosphoric Monoester Hydrolases Pedigree Paresis 030104 developmental biology Peripheral neuropathy Muscle Spasticity Child Preschool Pediatrics Perinatology and Child Health Disease Progression Female Neurology (clinical) medicine.symptom business Metabolism Inborn Errors 030217 neurology & neurosurgery |
| Zdroj: | Neuropediatrics, 49(5), 330-338. Hippokrates Verlag GmbH Alhaddad, B, Schossig, A, Haack, T B, Kovács-Nagy, R, Braunisch, M C, Makowski, C, Senderek, J, Vill, K, Müller-Felber, W, Strom, T M, Krabichler, B, Freisinger, P, Deshpande, C, Polster, T, Wolf, N I, Desguerre, I, Wörmann, F, Rötig, A, Ahting, U, Kopajtich, R, Prokisch, H, Meitinger, T, Feichtinger, R G, Mayr, J A, Jungbluth, H, Hubmann, M, Zschocke, J, Distelmaier, F & Koch, J 2018, ' PRUNE1 Deficiency: Expanding the Clinical and Genetic Spectrum ', Neuropediatrics, vol. 49, no. 5, pp. 330-338 . https://doi.org/10.1055/s-0038-1661396 |
| ISSN: | 1439-1899 0174-304X |
| DOI: | 10.1055/s-0038-1661396 |
| Popis: | Background Primary microcephaly and profound global developmental delay have been considered the core clinical phenotype in patients with bi-allelic PRUNE1 mutations. Methods Linkage analysis and whole-exome sequencing (WES) in a multiplex family and extraction of further cases from a WES repository containing 571 children with severe developmental disabilities and neurologic symptoms. Results We identified bi-allelic PRUNE1 mutations in twelve children from six unrelated families. All patients who survived beyond the first 6 months of life had early-onset global developmental delay, bilateral spastic paresis, dysphagia and difficult-to-treat seizures, while congenital or later-evolving microcephaly was not a consistent finding. Brain MRI showed variable anomalies with progressive cerebral and cerebellar atrophies and T2-hyperintense brain stem lesions. Peripheral neuropathy was documented in five cases. Disease course was progressive in all patients and eight children died in the first or early second decade of life. In addition to the previously reported missense mutation p.(Asp106Asn), we observed a novel homozygous missense variant p.(Leu172Pro) and a homozygous contiguous gene deletion encompassing most of the PRUNE1 gene and part of the neighboring BNIPL gene. Conclusions PRUNE1 deficiency causes severe early-onset disease affecting the central and peripheral nervous systems. Microcephaly is probably not a universal feature. |
| Databáze: | OpenAIRE |
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