Journal article

Authors list: Volk, Alexander E.; Hedergott, Andrea; Preising, Markus; Rading, Sebastian; Fricke, Julia; Herkenrath, Peter; Nurnberg, Peter; Altmueller, Janine; von Ameln, Simon; Lorenz, Birgit; Neugebauer, Antje; Karsak, Meliha; Kubisch, Christian

Publication year: 2021

Pages: 1157-1168

Journal: Human Genetics

Volume number: 140

Issue number: 8

ISSN: 0340-6717

eISSN: 1432-1203

DOI Link: https://doi.org/10.1007/s00439-021-02285-0

Publisher: Springer

Abstract: 
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.

Harvard Citation style: Volk, A., Hedergott, A., Preising, M., Rading, S., Fricke, J., Herkenrath, P., et al. (2021) Biallelic mutations in l-dopachrome tautomerase (DCT) cause infantile nystagmus and oculocutaneous albinism, Human Genetics, 140(8), pp. 1157-1168. https://doi.org/10.1007/s00439-021-02285-0

APA Citation style: Volk, A., Hedergott, A., Preising, M., Rading, S., Fricke, J., Herkenrath, P., Nurnberg, P., Altmueller, J., von Ameln, S., Lorenz, B., Neugebauer, A., Karsak, M., & Kubisch, C. (2021). Biallelic mutations in l-dopachrome tautomerase (DCT) cause infantile nystagmus and oculocutaneous albinism. Human Genetics. 140(8), 1157-1168. https://doi.org/10.1007/s00439-021-02285-0