Elsevier

Ophthalmology

Volume 107, Issue 1, January 2000, Pages 55-61
Ophthalmology

Article for CME Credit
Autosomal dominant cone–rod retinal dystrophy (CORD6) from heterozygous mutation of GUCY2D, which encodes retinal guanylate cyclase1,

https://doi.org/10.1016/S0161-6420(99)00038-XGet rights and content

Abstract

Objective

To describe the clinical features of autosomal dominant cone–rod retinal dystrophy (CRD) in a British family mapping to chromosome 17p12-p13 (CORD6), with a heterozygous mutation (Glu837Asp/Arg838Ser) of GUCY2D.

Design

A prospective, clinical family survey.

Patients

Ten affected members of a family with autosomal dominant CRD.

Methods

Full clinical examinations were undertaken. Selected affected family members underwent electrophysiologic evaluation, scotopic static perimetry, dark adaptometry, and color vision assessment.

Main outcome measures

Clinical appearance and electroretinographic responses.

Results

Typical clinical and electroretinographic features of childhood-onset CRD were recorded. In addition, moderate myopia and pendular nystagmus were seen in affected individuals. Color vision assessment in the youngest affected individual showed no color discrimination on a tritan axis, but retention of significant red–green discrimination. Electronegative electroretinogram responses were seen on electrophysiology in the only young family member examined.

Conclusions

The phenotype associated with GUCY2D CRD is clinically distinct from that associated with other dominant CRD loci. Unusual electroretinographic responses may indicate that this mutation of GUCY2D is associated with early defects in photoreceptor synaptic transmission to second-order neurons.

Section snippets

Patients

Twenty-seven members of the family originally linked to CORD67(Fig 1) were contacted and enrolled into a clinical and molecular genetic study. Eleven members (one from historical records only) were found to have clinical features of CRD. Local ethical committee approval and informed consent for clinical investigations was obtained from all enrolled participants before the study.

Molecular genetics

Molecular genetic study has established that CRD in this family is associated with a heterozygous alteration of GUCY2D

Results

Table 1lists clinical and electrophysiologic features identified in affected individuals studied. One patient declined examination but did supply clinical information that was consistent with affected status. Early-onset disease was reported by all affected individuals: all were aware of poor vision before 6 years of age. Marked photophobia was reported in several affected individuals. Peripheral field loss and nyctalopia were not reported until the fourth decade of life, and significantly, the

Discussion

Four genomic loci have now been implicated in the cause of autosomal dominant CRD, each with differentiating clinical features. Adult-onset CRD has been documented for the CORD7 locus8 and with mutations of CRX (Glu168delΔ1bp,3 Glu80Ala,3 Arg41Trp,34 Arg41Gln,34 Val242Met,34 196/7delΔ4bp34) at the CORD2 locus. The original CORD2-linked CRD family,19 in which disease progresses to no light perception by middle age, is not associated with a CRX mutation.35 Szlyk et al36 have subclassified CRD

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    Supported by the TFC Frost Charitable Trust, the Foundation Fighting Blindness, and the Wellcome Trust (grant no.: 041905).

    1

    The authors have no proprietary interests in the materials mentioned in the study.

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