Genetic heterogeneity of dominant optic atrophy, Kjer type: Identification of a second locus on chromosome 18q12.2-12.3.

OBJECTIVE: To evaluate a family with autosomal dominant optic atrophy, which has been previously linked to the Kidd blood group. DESIGN: Clinical evaluation with the assessment of visual acuity, color vision, and optic nerve appearance to determine affection status. Linkage analysis using polymorphic DNA markers. RESULTS: Visual acuities ranged from 20/20 to 6/200. Although linkage was excluded for chromosome 3q28-29, markers from chromosome 18 in the vicinity of the Kidd locus were linked to the disorder (D18S34 [maximal lod score (lodmax) of 5.38 at recombination fraction (theta) of 0.14], D18S548 [lod(max)=7.26, theta=0.09], D18S861 [lod(max)= 5.32, theta = 0.07], and D18S479 [lod(max) = 3.28, 0 = 0.12:]). Multipoint linkage analysis demonstrated lod scores of greater than 3 in an approximately 3-centimorgan region flanked by D18S34 and D18S479, using 98% penetrance and a phenocopy rate of 1/50. CONCLUSIONS: Dominant optic atrophy is genetically heterogeneous, with loci assigned to chromosomes 3q28-29 and 18q12.2-12.3. Dominant optic atrophy linked to 18q shows intrafamilial variation similar to that previously reported in families linked to 3q, with visual acuities ranging from normal to legal blindness. The overall distribution of visual acuities appears more favorable with the 18q phenotype. Both phenotypes appear to have a similar rate of visual decline.

Clinical features of autosomal dominant congenital nystagmus linked to chromosome 6p12.

PURPOSE: To describe the clinical features of a large pedigree with autosomal dominant congenital nystagmus linked to chromosome 6p12. METHODS: In a prospective evaluation of 54 living family members in a single pedigree, 21 persons were affected with autosomal dominant congenital nystagmus, and clinical examinations were performed on 14. Selected persons underwent further studies, including electroretinography, scanning laser ophthalmoscopy, nerve fiber layer studies, visual evoked potential studies, and eye movement recordings. RESULTS: Among seven affected persons whose parents were able to report whether the nystagmus was present congenitally, onset at birth was noted in two persons and between 3 and 6 months in five persons. Best-corrected binocular Snellen visual acuity ranged from 20/30 to 20/100, with a mode of 20/50. Strabismus was present in 14 examined patients (36%). Eye movement recordings, performed on five persons, included asymmetric pendular (three), asymmetric pendular combined with dual waveform jerk (one), and unidirectional jerk nystagmus (one). CONCLUSIONS: Autosomal dominant congenital nystagmus represents a disorder with variable expressivity. While onset is typically during infancy, it can be noted at birth. Intrafamilial variation in visual acuity, ocular alignment, and nystagmus waveform suggests a role for modifying influences on expression of disease.

[Retinal occlusive vasculopathy and primary anti-phospholipid syndrome: when to evoke it?]. / Vasculopathie occlusive rétinienne et syndrome anti-phospholipide primaire: quand l'évoquer?

A severe case of retinal vascular occlusion in a 31 year old white female is reported. Its origin is attributed to the primary antiphospholipid syndrome. The diagnostic criteria and the treatment of the primary antiphospholipid syndrome are revised and discussed. When the etiology of a retinal vascular occlusion is not assessed by the initial work-up, especially if the initial presentation consists of a severe occlusive disease, antiphospholipid antibodies should be checked.

A gene for autosomal dominant congenital nystagmus localizes to 6p12.

Congenital nystagmus is an idiopathic disorder characterized by bilateral ocular oscillations usually manifest during infancy. Vision is typically decreased due to slippage of images across the fovea. As such, visual acuity correlates with nystagmus intensity, which is the amplitude and frequency of eye movements at a given position of gaze. X-linked, autosomal dominant, and autosomal recessive pedigrees have been described, but no mapping studies have been published. We recently described a large pedigree with autosomal dominant congenital nystagmus. A genome-wide search resulted in six markers on 6p linked by two-point analysis at theta = 0 (D6S459, D6S452, D6S465, FTHP1, D6S257, D6S430). Haplotype analysis localizes the gene for autosomal dominant congenital motor nystagmus to an 18-cM region between D6S271 and D6S455.