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A Rare Mutation in The APOB Gene Associated with Neurological Manifestations in Familial Hypobetalipoproteinemia.
Musialik, Joanna; Boguszewska-Chachulska, Anna; Pojda-Wilczek, Dorota; Gorzkowska, Agnieszka; Szymanczak, Robert; Kania, Magdalena; Kujawa-Szewieczek, Agata; Wojcieszyn, Malgorzata; Hartleb, Marek; Wiecek, Andrzej.
Afiliação
  • Musialik J; Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, 40-055 Katowice, Poland.
  • Boguszewska-Chachulska A; Genomed SA, 02-971 Warsaw, Poland.
  • Pojda-Wilczek D; Department of Ophthalmology, Medical University of Silesia in Katowice, 40-055 Katowice, Poland.
  • Gorzkowska A; Department of Neurology, Department of Neurorehabilitation, Medical University of Silesia in Katowice, 40-055 Katowice, Poland.
  • Szymanczak R; Genomed SA, 02-971 Warsaw, Poland.
  • Kania M; Genomed SA, 02-971 Warsaw, Poland.
  • Kujawa-Szewieczek A; Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, 40-055 Katowice, Poland.
  • Wojcieszyn M; Department of Gastroenterology, II John Paul Pediatric Center, 41-200 Sosnowiec, Poland.
  • Hartleb M; Department of Gastroenterology and Hepatology, Medical University of Silesia in Katowice, 40-055 Katowice, Poland.
  • Wiecek A; Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, 40-055 Katowice, Poland.
Int J Mol Sci ; 21(4)2020 Feb 20.
Article em En | MEDLINE | ID: mdl-32093271
ABSTRACT
Clinical phenotypes of familial hypobetalipoproteinemia (FHBL) are related to a number of defective apolipoprotein B (APOB) alleles. Fatty liver disease is a typical manifestation, but serious neurological symptoms can appear. In this study, genetic analysis of the APOB gene and ophthalmological diagnostics were performed for family members with FHBL. Five relatives with FHBL, including a proband who developed neurological disorders, were examined. A sequencing analysis of the whole coding region of the APOB gene, including flanking intronic regions, was performed using the next-generation sequencing (NGS) method. Electrophysiological ophthalmological examinations were also done. In the proband and his affected relatives, NGS identified the presence of the pathogenic, rare heterozygous splicing variant c.3696+1G>T. Two known heterozygous missense variants-c.2188G>A, p.(Val730Ile) and c.8353A>C, p.(Asn2785His)-in the APOB gene were also detected. In all patients, many ophthalmologic abnormalities in electrophysiological tests were also found. The identified splicing variant c.3696+1G>T can be associated with observed autosomal, dominant FHBL with coexisting neurological symptoms, and both identified missense variants could be excluded as the main cause of observed clinical signs, according to mutation databases and the literature. Electroretinography examination is a sensitive method for the detection of early neuropathy and should therefore be recommended for the care of patients with FHBL.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Splicing de RNA / Mutação de Sentido Incorreto / Hipobetalipoproteinemia Familiar por Apolipoproteína B / Apolipoproteína B-100 / Doenças do Sistema Nervoso Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Splicing de RNA / Mutação de Sentido Incorreto / Hipobetalipoproteinemia Familiar por Apolipoproteína B / Apolipoproteína B-100 / Doenças do Sistema Nervoso Idioma: En Ano de publicação: 2020 Tipo de documento: Article