PMID- 33100333
OWN - NLM
STAT- MEDLINE
DCOM- 20210603
LR  - 20230816
IS  - 1530-0366 (Electronic)
IS  - 1098-3600 (Linking)
VI  - 23
IP  - 3
DP  - 2021 Mar
TI  - Dopachrome tautomerase variants in patients with oculocutaneous albinism.
PG  - 479-487
LID - 10.1038/s41436-020-00997-8 [doi]
AB  - PURPOSE: Albinism is a clinically and genetically heterogeneous condition. 
      Despite analysis of the 20 known genes, ~30% patients remain unsolved. We aimed 
      to identify new genes involved in albinism. METHODS: We sequenced a panel of 
      genes with known or predicted involvement in melanogenesis in 230 unsolved 
      albinism patients. RESULTS: We identified variants in the Dopachrome tautomerase 
      (DCT) gene in two patients. One was compound heterozygous for a 14-bp deletion in 
      exon 9 and c.118T>A p.(Cys40Ser). The second was homozygous for c.183C>G 
      p.(Cys61Trp). Both patients had mild hair and skin hypopigmentation, and 
      classical ocular features. CRISPR-Cas9 was used in C57BL/6J mice to create 
      mutations identical to the missense variants carried by the patients, along with 
      one loss-of-function indel. When bred to homozygosity the three mutations 
      revealed hypopigmentation of the coat, milder for Cys40Ser compared with Cys61Trp 
      or the frameshift mutation. Histological analysis identified significant 
      hypopigmentation of the retinal pigmented epithelium (RPE) indicating that 
      defective RPE melanogenesis could be associated with eye and vision defects. DCT 
      loss of function in zebrafish embryos elicited hypopigmentation both in 
      melanophores and RPE cells. CONCLUSION: DCT is the gene for a new type of 
      oculocutaneous albinism that we propose to name OCA8.
FAU - Pennamen, Perrine
AU  - Pennamen P
AD  - Rare Diseases, Genetics and Metabolism, INSERM U1211, University of Bordeaux, 
      Bordeaux, France.
AD  - Molecular Genetics Laboratory, Bordeaux University Hospital, Bordeaux, France.
FAU - Tingaud-Sequeira, Angele
AU  - Tingaud-Sequeira A
AD  - Rare Diseases, Genetics and Metabolism, INSERM U1211, University of Bordeaux, 
      Bordeaux, France.
FAU - Gazova, Iveta
AU  - Gazova I
AD  - MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK.
FAU - Keighren, Margaret
AU  - Keighren M
AD  - MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK.
FAU - McKie, Lisa
AU  - McKie L
AD  - MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK.
FAU - Marlin, Sandrine
AU  - Marlin S
AD  - Laboratory of Embryology and Genetics of Human Malformation, Imagine Institute, 
      Paris Descartes, Sorbonne Paris Cite University, Paris, France.
FAU - Gherbi Halem, Souad
AU  - Gherbi Halem S
AD  - Laboratory of Embryology and Genetics of Human Malformation, Imagine Institute, 
      Paris Descartes, Sorbonne Paris Cite University, Paris, France.
FAU - Kaplan, Josseline
AU  - Kaplan J
AD  - Laboratory of Genetics in Ophthalmology, Imagine Institute, Paris Descartes, 
      Sorbonne Paris Cite University, Paris, France.
FAU - Delevoye, Cedric
AU  - Delevoye C
AD  - Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane 
      Compartments, Paris, France.
FAU - Lacombe, Didier
AU  - Lacombe D
AD  - Rare Diseases, Genetics and Metabolism, INSERM U1211, University of Bordeaux, 
      Bordeaux, France.
FAU - Plaisant, Claudio
AU  - Plaisant C
AD  - Molecular Genetics Laboratory, Bordeaux University Hospital, Bordeaux, France.
FAU - Michaud, Vincent
AU  - Michaud V
AD  - Molecular Genetics Laboratory, Bordeaux University Hospital, Bordeaux, France.
FAU - Lasseaux, Eulalie
AU  - Lasseaux E
AD  - Molecular Genetics Laboratory, Bordeaux University Hospital, Bordeaux, France.
FAU - Javerzat, Sophie
AU  - Javerzat S
AD  - Rare Diseases, Genetics and Metabolism, INSERM U1211, University of Bordeaux, 
      Bordeaux, France.
FAU - Jackson, Ian
AU  - Jackson I
AD  - MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK.
AD  - Roslin Institute, University of Edinburgh, Edinburgh, UK.
FAU - Arveiler, Benoit
AU  - Arveiler B
AUID- ORCID: 0000-0002-2987-2932
AD  - Rare Diseases, Genetics and Metabolism, INSERM U1211, University of Bordeaux, 
      Bordeaux, France. benoit.arveiler@chu-bordeaux.fr.
AD  - Molecular Genetics Laboratory, Bordeaux University Hospital, Bordeaux, France. 
      benoit.arveiler@chu-bordeaux.fr.
LA  - eng
GR  - MC_UU_00007/4/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201026
PL  - United States
TA  - Genet Med
JT  - Genetics in medicine : official journal of the American College of Medical 
      Genetics
JID - 9815831
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.3.12 (dopachrome isomerase)
SB  - IM
CIN - Pigment Cell Melanoma Res. 2021 Jan;34(1):10-12. PMID: 32969584
MH  - *Albinism, Oculocutaneous/genetics
MH  - Animals
MH  - Humans
MH  - Intramolecular Oxidoreductases
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutation
MH  - *Zebrafish
OTO - NOTNLM
OT  - DCT
OT  - albinism
OT  - mouse
OT  - pigmentation
OT  - zebrafish.
EDAT- 2020/10/27 06:00
MHDA- 2021/06/04 06:00
CRDT- 2020/10/26 05:18
PHST- 2020/06/26 00:00 [received]
PHST- 2020/09/24 00:00 [accepted]
PHST- 2020/09/24 00:00 [revised]
PHST- 2020/10/27 06:00 [pubmed]
PHST- 2021/06/04 06:00 [medline]
PHST- 2020/10/26 05:18 [entrez]
AID - S1098-3600(21)04940-6 [pii]
AID - 10.1038/s41436-020-00997-8 [doi]
PST - ppublish
SO  - Genet Med. 2021 Mar;23(3):479-487. doi: 10.1038/s41436-020-00997-8. Epub 2020 Oct 
      26.