Your browser doesn't support javascript.
loading
Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations.
Madhu, Rajesh; Beaman, Glenda M; Chandler, Kate E; O'Sullivan, James; Urquhart, Jill E; Khan, Naz; Martindale, Elizabeth; Briggs, Tracy A; Clayton-Smith, Jill; Higgs, Jenny; Batra, Gauri; Kerr, Bronwyn; Woolf, Adrian S; Newman, William G.
Afiliação
  • Madhu R; Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Paediatric Neurosciences Department, Alder Hey Children's Hospital NHS Foundation Trust, Liverpool, UK.
  • Beaman GM; Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
  • Chandler KE; Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
  • O'Sullivan J; Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
  • Urquhart JE; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
  • Khan N; Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
  • Martindale E; Department of Obstetrics and Gynaecology, Royal Blackburn Hospital, Blackburn, UK.
  • Briggs TA; Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
  • Clayton-Smith J; Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
  • Higgs J; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK; Liverpool Centre for Genomic Medicine, Liverpool Women's Hospital, Liverpool, UK.
  • Batra G; Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
  • Kerr B; Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
  • Woolf AS; Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester, UK; Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
  • Newman WG; Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK. Electronic address: william.newman@manchester.ac.uk.
Eur J Med Genet ; 63(9): 103974, 2020 Sep.
Article em En | MEDLINE | ID: mdl-32534991
Ligase IV (LIG4) syndrome is a rare disorder of DNA damage repair caused by biallelic, pathogenic variants in LIG4. This is a phenotypically heterogeneous condition with clinical presentation varying from lymphoreticular malignancies in developmentally normal individuals to significant microcephaly, primordial dwarfism, radiation hypersensitivity, severe combined immunodeficiency and early mortality. Renal defects have only rarely been described as part of the ligase IV disease spectrum. We identified a consanguineous family where three siblings presenting with antenatal growth retardation, microcephaly, severe renal anomalies and skeletal abnormalities, including radial ray defects. Autozygosity mapping and exome sequencing identified a novel homozygous frameshift variant in LIG4, c.597_600delTCAG, p.(Gln200LysfsTer33), which segregated in the family. LIG4 is encoded by a single exon and so this frameshift variant is predicted to result in a protein truncated by 678 amino acids. This is the shortest predicted LIG4 protein product reported and correlates with the most severe clinical phenotype described to date. We note the clinical overlap with Fanconi anemia and suggest that LIG4 syndrome is considered in the differential diagnosis of this severe developmental disorder.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenótipo / Rádio (Anatomia) / Anormalidades Craniofaciais / Rim Displásico Multicístico / Anemia de Fanconi / DNA Ligase Dependente de ATP / Transtornos do Crescimento / Síndromes de Imunodeficiência / Microcefalia Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenótipo / Rádio (Anatomia) / Anormalidades Craniofaciais / Rim Displásico Multicístico / Anemia de Fanconi / DNA Ligase Dependente de ATP / Transtornos do Crescimento / Síndromes de Imunodeficiência / Microcefalia Idioma: En Ano de publicação: 2020 Tipo de documento: Article