Biallelic mutations in L-dopachrome tautomerase (DCT) cause infantile nystagmus and oculocutaneous albinism

Hum Genet. 2021 Aug;140(8):1157-1168. doi: 10.1007/s00439-021-02285-0. Epub 2021 May 6.


Infantile nystagmus syndrome (INS) denominates early-onset, involuntary oscillatory eye movements with different etiologies. Nystagmus is also one of the symptoms in oculocutaneus albinism (OCA), a heterogeneous disease mainly caused by defects in melanin synthesis or melanosome biogenesis. Dopachrome tautomerase (DCT, also called TYRP2) together with tyrosinase (TYR) and tyrosin-related protein 1 (TYRP1) is one of the key enzymes in melanin synthesis. Although DCT´s role in pigmentation has been proven in different species, until now only mutations in TYR and TYRP1 have been found in patients with OCA. Detailed ophthalmological and orthoptic investigations identified a consanguineous family with two individuals with isolated infantile nystagmus and one family member with subtle signs of albinism. By whole-exome sequencing and segregation analysis, we identified the missense mutation c.176G > T (p.Gly59Val) in DCT in a homozygous state in all three affected family members. We show that this mutation results in incomplete protein maturation and targeting in vitro compatible with a partial or total loss of function. Subsequent screening of a cohort of patients with OCA (n = 85) and INS (n = 25) revealed two heterozygous truncating mutations, namely c.876C > A (p.Tyr292*) and c.1407G > A (p.Trp469*), in an independent patient with OCA. Taken together, our data suggest that mutations in DCT can cause a phenotypic spectrum ranging from isolated infantile nystagmus to oculocutaneous albinism.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Albinism, Oculocutaneous / diagnosis
  • Albinism, Oculocutaneous / enzymology
  • Albinism, Oculocutaneous / genetics*
  • Albinism, Oculocutaneous / pathology
  • Base Sequence
  • Calnexin / genetics
  • Calnexin / metabolism
  • Child
  • Cohort Studies
  • Consanguinity
  • Exome Sequencing
  • Female
  • Gene Expression Regulation
  • HEK293 Cells
  • Homozygote
  • Humans
  • Intramolecular Oxidoreductases / deficiency
  • Intramolecular Oxidoreductases / genetics*
  • Male
  • Melanins / biosynthesis*
  • Melanins / genetics
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Mutation, Missense*
  • Nystagmus, Congenital / diagnosis
  • Nystagmus, Congenital / enzymology
  • Nystagmus, Congenital / genetics*
  • Nystagmus, Congenital / pathology
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Pedigree
  • Young Adult


  • CANX protein, human
  • Melanins
  • Membrane Glycoproteins
  • Calnexin
  • Oxidoreductases
  • TYRP1 protein, human
  • Monophenol Monooxygenase
  • Intramolecular Oxidoreductases
  • dopachrome isomerase