Universität zu Köln

Khan, Arif O., Al-Mesfer, Saleh, Al-Turkmani, Shahira, Bergmann, Carsten and Bolz, Hanno J. (2014). Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay. Br. J. Ophthalmol., 98 (12). S. 1724 - 1729. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2079

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Abstract

Background Leber congenital amaurosis (LCA) is a severe infantile retinal dystrophy that is non-syndromic other than neurodevelopmental delay, reported in up to 20% of cases according to one older study. The phenotype is typically autosomal recessive and is genetically heterogeneous. Although LCA is defined by a non-recordable electroretinogram (ERG) during infancy, many LCA studies include infants with low ERG readings and/or older children not phenotyped during infancy. More recent series of genetically confirmed LCA do not document the recurrent neurodevelopmental delay of older studies. We investigate the possibility that neurodevelopmental delay is not actually a recurrent feature of strictly defined otherwise non-syndromic LCA. Methods Retrospective consecutive case series (2012-2014) of children with strictly defined LCA, all of whom underwent targeted next-generation sequencing with a panel of 14 LCA genes. Results All families were endogamous and/or consanguineous. 18/19 (22/23 children) had detectable causative recessive mutations, and these were in one of three genes only: 11 in RPGRIP1, 5 in GUCY2D and 2 in RPE65. 9/11 children with RPGRIP1 mutations harboured homozygous c. 1007delA (p.Glu370Asnfs*5) mutation. 5/23 children (22%) had concomitant neurodevelopmental delay, and these five children harboured recessive mutations in RPGRIP1 (2) or GUCY2D (3). Haplotype analysis for cases with the RPGRIP1 deletion suggested a single ancestral mutation. Conclusions Neurodevelopmental delay is a potential feature of strictly defined LCA, documented in our series for some children with homozygous RPGRIP1 and GUCY2D mutations. Strictly defining LCA can limit genetic heterogeneity. On the Arabian Peninsula, the phenotype is frequently from recessive RPGRIP1 mutations, most of which are a founder RPGRIP1 deletion.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Khan, Arif O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Al-Mesfer, Saleh UNSPECIFIED UNSPECIFIED UNSPECIFIED Al-Turkmani, Shahira UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergmann, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolz, Hanno J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-422084
DOI:	10.1136/bjophthalmol-2014-305122
Journal or Publication Title:	Br. J. Ophthalmol.
Volume:	98
Number:	12
Page Range:	S. 1724 - 1729
Date:	2014
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1468-2079
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RETINITIS-PIGMENTOSA; RETINAL DYSTROPHY; MUTATION ANALYSIS; DISEASE; POPULATION; DIAGNOSIS; PHENOTYPE; CEP290; RPE65 Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42208