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Germline variants in oculocutaneous albinism genes and predisposition to familial cutaneous melanoma

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features and clinical outcome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Genetics of familial melanoma: 20 years after CDKN2A

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Increasing the complexity: new genes and new types of albinism

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. A cryptic BAP1 splice mutation in a family with uveal and cutaneous melanoma, and paraganglioma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. The molecular profile of mucosal melanoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. A rare missense variant in APC interrupts splicing and causes AFAP in two Danish families

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Vaishnavi Nathan
  • Peter A Johansson
  • Jane M Palmer
  • Madeleine Howlie
  • Hayley R Hamilton
  • Karin Wadt
  • Göran Jönsson
  • Kelly M Brooks
  • Antonia L Pritchard
  • Nicholas K Hayward
Vis graf over relationer

Approximately 1%-2% of cutaneous melanoma (CM) is classified as strongly familial. We sought to investigate unexplained CM predisposition in families negative for the known susceptibility genes using next-generation sequencing of affected individuals. Segregation of germline variants of interest within families was assessed by Sanger sequencing. Several heterozygous variants in oculocutaneous albinism (OCA) genes: TYR, OCA2, TYRP1 and SLC45A2, were present in our CM cohort. OCA is a group of autosomal recessive genetic disorders, resulting in pigmentation defects of the eyes, hair and skin. Missense variants classified as pathogenic for OCA were present in multiple families and some fully segregated with CM. The functionally compromised TYR p.T373K variant was present in three unrelated families. In OCA2, known pathogenic variants: p.V443I and p.N489D, were present in three families and one family, respectively. We identified a likely pathogenic SLC45A2 frameshift variant that fully segregated with CM in a family of four cases. Another four-case family harboured cosegregating variants (p.A24T and p.R153C) of uncertain functional significance in TYRP1. We conclude that rare, heterozygous variants in OCA genes confer moderate risk for CM.

OriginalsprogEngelsk
TidsskriftPigment Cell & Melanoma Research
Vol/bind32
Udgave nummer6
Sider (fra-til)854-863
Antal sider10
ISSN1755-1471
DOI
StatusUdgivet - nov. 2019

Bibliografisk note

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

ID: 59279913