Universität zu Köln

Volk, Alexander E., Hedergott, Andrea ORCID: 0000-0002-6398-3919, Preising, Markus, Rading, Sebastian, Fricke, Julia, Herkenrath, Peter, Nurnberg, Peter, Altmueller, Janine, von Ameln, Simon, Lorenz, Birgit, Neugebauer, Antje, Karsak, Meliha and Kubisch, Christian (2021). Biallelic mutations in l-dopachrome tautomerase (DCT) cause infantile nystagmus and oculocutaneous albinism. Hum. Genet., 140 (8). S. 1157 - 1169. NEW YORK: SPRINGER. ISSN 1432-1203

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Volk, Alexander E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hedergott, Andrea UNSPECIFIED orcid.org/0000-0002-6398-3919 UNSPECIFIED Preising, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Rading, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Fricke, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Herkenrath, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Nurnberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED von Ameln, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Lorenz, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Neugebauer, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Karsak, Meliha UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubisch, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-593657
DOI:	10.1007/s00439-021-02285-0
Journal or Publication Title:	Hum. Genet.
Volume:	140
Number:	8
Page Range:	S. 1157 - 1169
Date:	2021
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CONGENITAL NYSTAGMUS; OCULAR ALBINISM; ISCEV STANDARD; TYROSINASE; IDENTIFICATION; GENES; TYR; PATHOGENICITY; MELANOCYTES; PREVALENCE Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59365