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Mild form of oculocutaneous albinism type 1: phenotypic analysis of compound heterozygous patients with the R402Q variant of the TYR gene
  1. Solene Monfermé1,
  2. Eulalie Lasseaux2,
  3. Catherine Duncombe-Poulet3,
  4. Christian Hamel4,
  5. Sabine Defoort-Dhellemmes5,
  6. Isabelle Drumare5,
  7. Xavier Zanlonghi6,
  8. Hélène Dollfus7,
  9. Yaurama Perdomo7,
  10. Dominique Bonneau8,
  11. Jean-François Korobelnik1,
  12. Claudio Plaisant2,
  13. Vincent Michaud2,
  14. Perrine Pennamen2,9,
  15. Caroline Rooryck-Thambo2,9,
  16. Fanny Morice-Picard10,
  17. Clement Paya11,
  18. Benoit Arveiler2,9
  1. 1 Service d’ophtalmologie, CHU de Bordeaux, Bordeaux, France
  2. 2 Service de génétique médicale, CHU de Bordeaux, Bordeaux, France
  3. 3 Cabinet d’ophtalmologie, rue du Château d’eau, Caen, France
  4. 4 Service d’ophtalmologie, Equipe maladies sensorielles génétiques, CHU de Montpellier, Montpellier, France
  5. 5 Service d’exploration de la vision et neuro-ophtalmologie, CHRU de Lille, Lille, France
  6. 6 Clinique ophtalmologique Sourdille, Nantes, France
  7. 7 Centre des affections rares en génétique ophtalmologique, CHU de Strasbourg, Strasbourg, France
  8. 8 Service de génétique, CHU d’Anger, Angers, France
  9. 9 INSERM U1211, Maladies Rares, Génétique et Métabolisme, Université de Bordeaux, Bordeaux, France
  10. 10 Service de dermatologie, Unité de dermato-pédiatrie du CHU de Bordeaux, Bordeaux, France
  11. 11 Centre d’ophtalmologie du Palais Gallien, Bordeaux, France
  1. Correspondence to Dr Solene Monfermé, Service d’ophtalmologie, CHU de Bordeaux, Bordeaux 33076, France; solene.monferme{at}


Aim Oculocutaneous albinism type 1 (OCA1) is due to TYR mutations. c.1205G>A/p.Arg402Gln (R402Q) is a thermosensitive variant of the TYR gene that has been reported to be responsible for mild forms of OCA1. The aim of our study was to define the phenotype associated with this variant.

Methods In our retrospective series, among 268 patients diagnosed with OCA1, 122 (45.5%) harboured one pathogenic variant of TYR, and the R402Q variant ensured to be in trans by segregation analysis in 69 patients (25.7%), constituting the ‘R402Q-OCA1’ group. 146 patients harboured two pathogenic variants of the TYR gene other than R402Q. Clinical records were available for 119 of them, constituting the ‘Classical-OCA1’ group.

Results Most R402Q-OCA1 patients presented with white or yellow-white hair at birth (71.43%), blond hair later (46.97%), a light phototype but with residual pigmentation (69.64%), and blue eyes (76.56%). Their pigmentation was significantly higher than in the classical-OCA1 group. All patients from the R402Q-OCA1 group presented with ocular features of albinism. However the prevalence of photophobia (78.13%) and iris transillumination (83.87%) and the severity scores of iris transillumination, retinal hypopigmentation and foveal hypoplasia were lower in the R402Q-OCA1 group. Visual acuity was higher in the R402Q-OCA1 group (0.38±0.21 logarithm of the minimum angle of resolution vs 0.76±0.24). Investigations concerning a possible additive effect of the c.575C>A/p.Ser192 (S192Y) variant of TYR in cis with R402Q, suggested by others, showed no significant impact on the phenotype.

Conclusion The R402Q variant leads to variable but generally mild forms of albinism whose less typical presentation may lead to underdiagnosis.

  • albinism
  • TYR gene
  • R402Q (c.1205G>A/p.Arg402Gln)
  • genotype-phenotype correlation
  • hypopigmentation
  • foveal hypoplasia
  • nystagmus
  • genotype-phenotype correlation

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  • Contributors All authors contributed to the acquisition, analysis or interpretation of data, reviewed the article and were involved in its drafting. BA, EL, SM, FM-P and CPa were responsible for the exact design of the study and for a substantial part of the redaction. All authors approved the version published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.