Universität zu Köln

Khan, A. O., Budde, B. S., Nuernberg, P., Kawalia, A., Lenzner, S. and Bolz, H. J. (2018). Genome-wide linkage and sequence analysis challenge CCDC66 as a human retinal dystrophy candidate gene and support a distinct NMNAT1-related fundus phenotype. Clin. Genet., 93 (1). S. 149 - 155. HOBOKEN: WILEY. ISSN 1399-0004

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Abstract

To uncover the genotype underlying early-onset cone-rod dystrophy and central nummular macular atrophic lesion in 2 siblings from an endogamous Arab family, we performed targeted next-generation sequencing (NGS) of 44 retinal dystrophy genes, whole-exome sequencing (WES) and genome-wide linkage analysis. Targeted NGS and WES in the index patient highlighted 2 homozygous variants, a CCDC66 frameshift deletion and a novel missense NMNAT1 variant, c.500G>A (p.Asn167Ser). Linkage and segregation analysis excluded the CCDC66 variant and confirmed the NMNAT1 mutation. Biallelic NMNAT1 mutations cause Leber congenital amaurosis with a central nummular macular atrophic lesion (LCA9). The NMNAT1 mutation reported here underlied cone-rod dystrophy rather than LCA but the fundus lesion was compatible with that of LCA9 patients, highlighting that such a fundus appearance should raise suspicion for biallelic mutations in NMNAT1 when in the context of any retinal dystrophy. Although Ccdc66 mutations have been proposed to cause retinal disease in dogs, our results and public databases challenge CCDC66 as a candidate gene for human retinal dystrophy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Khan, A. O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Budde, B. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kawalia, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lenzner, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolz, H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-204873
DOI:	10.1111/cge.13022
Journal or Publication Title:	Clin. Genet.
Volume:	93
Number:	1
Page Range:	S. 149 - 155
Date:	2018
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1399-0004
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LEBER CONGENITAL AMAUROSIS; NMNAT1 MUTATIONS; DISEASE Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20487