UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause Schnyder Corneal Dystrophy

Peer reviewe

UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause Schnyder Corneal Dystrophy

Abstract Background: Mutations in a novel gene, UBIAD1, were recently found to cause the autosomal dominant eye disease Schnyder corneal dystrophy (SCD). SCD is characterized by an abnormal deposition of cholesterol and phospholipids in the cornea resulting in progressive corneal opacification and visual loss. We characterized lesions in the UBIAD1 gene in new SCD families and examined protein homology, localization, and structure

Lhermitte-Duclos disease in 3 children: A clinical long-term observation

We report three boys in whom a diagnosis of Lhermitte-Duclos disease (LDD) was assumed from characteristic neuroimaging findings. LDD was confirmed by an open biopsy in patient 1, while a biopsy in patient 2 was inconclusive. Histologic confirmation in patient 3 was deliberately not attempted. However, a follow-up observation of stable clinical and neuroimaging findings over 2, 5 and 11 years, respectively, support the diagnosis of LDD. Despite extensive expansion of the lesion with brainstem involvement, clinical signs in two boys were minimal, while one patient has cognitive impairment and a complex oculomotor disturbance. So far we found no evidence for an association with Cowden disease (CD). No germline PTEN mutations were detected in these children, but the amount of available biopsy tissue in patients 1 and 2 was insufficient for a complete genetic analysis of tumor tissue. In conclusion, LDD can usually be diagnosed by MRI. In view of the favourable natural history, a conservative “wait and see” strategy is justified, particularly if radical tumor resection is not possible. LDD is often not associated with CD and germline PTEN mutations seem not to be present in isolated LDD

Ophthalmologe

Background Schnyder's crystalline corneal dystrophy (SCCD) is a rare autosomal dominant disease and can occur in association with hyperlipoproteinemia. The disease has been mapped to chromosome 1p34.1–p36. Case report We report on a 66-year-old woman and her son with Schnyder's crystalline corneal dystrophy. The mother had type IV hyperlipoproteinemia and hypercholesterolemia while her son had hypercholesterolemia with elevated LDL-cholesterol. Analysis of microsatellite markers within the candidate interval of 1p34.1–p36 showed that the affected son and his unaffected brother had inherited different alleles only for the proximal marker D1S228 from their affected mother. Conclusions The haplotype analysis suggests that either recombination has occurred, which would allow the candidate interval to be narrowed down, or alternatively, the SCCD in the reported family is not linked to chromosome 1, which would be a first indication of genetic heterogeneity in this disease. To reduce the risk of cardiovascular disease, hyperlipidemia should always be excluded in patients with Schnyder's crystalline corneal dystrophy