title: Absence of ocular manifestations in autosomal dominant Alport syndrome associated with haematological abnormalties.
abstract: Most patients with Alport syndrome have X-linked or autosomal recessive disease that is characterised by renal failure, hearing loss, and, in nearly 75% of the cases, a dot-and-fleck retinopathy and anterior lenticonus. There are only case reports of individuals with the rare autosomal dominant form, who can have haematuria or renal failure, deafness, and, in addition, low platelet counts and neutrophil inclusions. The ocular features of autosomal dominant inheritance have not been described. We have examined the eyes in the members of two families where Alport syndrome was diagnosed on the basis of the clinical features and family history, and where autosomal dominant inheritance was confirmed by father-to-son disease transmission, the associated haematological abnormalities, and haplotypes that segregated with the recently described locus at chromosome 22q. In Family A, the eyes of two individuals with haematuria, hearing loss, and haematological abnormalities and of nine unaffected family members were examined. In Family B, the eyes of two individuals with renal failure, normal hearing, and haematological abnormalities were examined. None of the affected or unaffected members in either family had a dot-and-fleck retinopathy, anterior lenticonus, a history suggesting recurrent corneal erosions, or corneal dystrophy. These results indicate that the protein abnormality in autosomal dominant Alport syndrome does not produce the retinopathy and lenticonus typical of X-linked and autosomal recessive disease. This may be because the abnormal protein is not present or is less important in the ocular basement membranes than elsewhere, or because the presence of a normal allele in autosomal dominant disease compensates for the defective allele.
authors.affiliation: Ophthalmology Unit, Austin and Repatriation Medical Centre, University of Melbourne Department of Medicine, Heidelberg, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Colville
authors.forename: Y Y
authors.initials: YY
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Jamieson
authors.forename: F
authors.initials: F
authors.lastname: Collins
authors.forename: J
authors.initials: J
authors.lastname: Hood
authors.forename: J
authors.initials: J
authors.lastname: Savige
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D005799:Genes, Dominant; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics; D006402:Hematologic Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006417:Hematuria / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007905:Lens Diseases / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D012164:Retinal Diseases / Q000175:diagnosis* / Q000209:etiology