Your browser doesn't support javascript.
loading
A patient with pontocerebellar hypoplasia type 6: Novel RARS2 mutations, comparison to previously published patients and clinical distinction from PEHO syndrome.
Nevanlinna, Viivi; Konovalova, Svetlana; Ceulemans, Berten; Muona, Mikko; Laari, Anni; Hilander, Taru; Gorski, Katarin; Valanne, Leena; Anttonen, Anna-Kaisa; Tyynismaa, Henna; Courage, Carolina; Lehesjoki, Anna-Elina.
Afiliación
  • Nevanlinna V; Folkhälsan Research Center, Helsinki, Finland; Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
  • Konovalova S; Research Programs Unit, University of Helsinki, Finland.
  • Ceulemans B; Department of Pediatric Neurology, Antwerp University Hospital, University of Antwerp, Belgium.
  • Muona M; Folkhälsan Research Center, Helsinki, Finland.
  • Laari A; Folkhälsan Research Center, Helsinki, Finland.
  • Hilander T; Research Programs Unit, University of Helsinki, Finland.
  • Gorski K; Folkhälsan Research Center, Helsinki, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland.
  • Valanne L; Department of Radiology, Hospital District of Helsinki and Uusimaa Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • Anttonen AK; Folkhälsan Research Center, Helsinki, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; Department of Clinical Genetics and Laboratory of Genetics, Helsinki University Hospital, Helsinki, Finland.
  • Tyynismaa H; Research Programs Unit, University of Helsinki, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland.
  • Courage C; Folkhälsan Research Center, Helsinki, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland.
  • Lehesjoki AE; Folkhälsan Research Center, Helsinki, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland. Electronic address: anna-elina.lehesjoki@helsinki.fi.
Eur J Med Genet ; 63(3): 103766, 2020 Mar.
Article en En | MEDLINE | ID: mdl-31536827
Pontocerebellar hypoplasia type 6 (PCH6) is a rare infantile-onset progressive encephalopathy caused by biallelic mutations in RARS2 that encodes the mitochondrial arginine-tRNA synthetase enzyme (mtArgRS). The clinical presentation overlaps that of PEHO syndrome (Progressive Encephalopathy with edema, Hypsarrhythmia and Optic atrophy). The proband presented with severe intellectual disability, epilepsy with varying seizure types, optic atrophy, axial hypotonia, acquired microcephaly, dysmorphic features and progressive cerebral and cerebellar atrophy and delayed myelination on MRI. The presentation had resemblance to PEHO syndrome but sequencing of ZNHIT3 did not identify pathogenic variants. Subsequent whole genome sequencing revealed novel compound heterozygous variants in RARS2, a missense variant affecting a highly conserved amino acid and a frameshift variant with consequent degradation of the transcript resulting in decreased mtArgRS protein level confirming the diagnosis of PCH6. Features distinguishing the proband's phenotype from PEHO syndrome were later appearance of hypotonia and elevated lactate levels in blood and cerebrospinal fluid. On MRI the proband presented with more severe supratentorial atrophy and lesser degree of abnormal myelination than PEHO syndrome patients. The study highlights the challenges in clinical diagnosis of patients with neonatal and early infantile encephalopathies with overlapping clinical features and brain MRI findings.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arginino-ARNt Ligasa / Atrofias Olivopontocerebelosas / Cerebelo Tipo de estudio: Prognostic_studies Límite: Humans / Infant / Male Idioma: En Revista: Eur J Med Genet Asunto de la revista: GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arginino-ARNt Ligasa / Atrofias Olivopontocerebelosas / Cerebelo Tipo de estudio: Prognostic_studies Límite: Humans / Infant / Male Idioma: En Revista: Eur J Med Genet Asunto de la revista: GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Países Bajos