Universität zu Köln

Hedergott, A., Volk, A. E., Herkenrath, P., Thiele, H., Fricke, J., Altmueller, J., Nuernberg, P., Kubisch, C. and Neugebauer, A. (2015). Clinical and genetic findings in a family with NMNAT1-associated Leber congenital amaurosis: case report and review of the literature. Graefes Arch. Clin. Exp. Ophthalmol., 253 (12). S. 2239 - 2247. NEW YORK: SPRINGER. ISSN 1435-702X

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Abstract

Leber congenital amaurosis (LCA) is a severe retinal dystrophy, typically manifesting in the first year of life. Mutations in more than 18 genes have been reported to date. In recent studies, biallelic mutations in NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 have been found to cause LCA. To broaden the knowledge regarding the phenotype of NMNAT1-associated LCA. Clinical ophthalmologic examinations were performed in two sisters with LCA. Whole exome sequencing was performed in one of the affected girls, with subsequent segregation analysis in the affected sister and unaffected parents. The literature was reviewed for reports of NMNAT1-associated LCA. Exome sequencing revealed the known NMNAT1 mutation c.25G > A (p.Val9Met) in a homozygous state. Segregation analysis showed the same homozygous mutation in the affected younger sister. Both parents were found to be heterozygous carriers of the mutation. The two girls both presented with severe visual impairment, nystagmus, central atrophy of the pigment epithelium, and pigment clumping in the periphery before the age of 6 months. Retinal vessels were attenuated. Both children were hyperopic. In the older sister, differential diagnosis included an inflammatory origin, but electrophysiology in her as well as her sister confirmed a diagnosis of LCA. Pallor of the optic nerve head was not present at birth but developed progressively. We confirmed a diagnosis of NMNAT1-associated LCA in two siblings through identification of the mutation (c.25G > A [p. Val9Met]) in a homozygous state. In infants with non-detectable electroretinogram (ERG), along with severe congenital visual dysfunction or blindness and central pigment epithelium atrophy with pigment clumping resembling scarring due to chorioretinitis, LCA due to NMNAT1 mutations should be considered.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hedergott, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Volk, A. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herkenrath, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fricke, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubisch, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neugebauer, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-385985
DOI:	10.1007/s00417-015-3174-0
Journal or Publication Title:	Graefes Arch. Clin. Exp. Ophthalmol.
Volume:	253
Number:	12
Page Range:	S. 2239 - 2247
Date:	2015
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1435-702X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUTATIONS; PHENOTYPE; WLD(S) Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38598