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Objective: To identify the disease-causing mutation in a family of Leber hereditary optic neuropathy (LHON)., Methods: Clinical data and family information were collected. Peripheral venous blood was drawn from patients and family members who agreed to donate the blood samples. Genomic DNA was extracted from blood leukocytes. Three primary mitochondrial DNA (mtDNA) mutations, G3460A, G11778A, and T14484C were screened using a method of polymerase chain reaction (PCR) followed by direct sequencing., Results: This 3-generation family had 14 members. Seven family members were affected, including 5 female patients and 2 male patients. Pedigree analysis showed maternal inheritance. Mutation analysis in 4 affected and 3 unaffected family members showed G11778A mutation in all 4 affected and 2 of the 3 unaffected individuals., Conclusions: G11778A mutation in mtDNA is the disease-causing mutation in this family of LHON. For the mutation carriers, early intervention may prevent or delay the onset of the disease.

Purpose: To identify CHST6 mutations in five additional Icelandic cases of macular corneal dystrophy (MCD) type I and in four families with MCD type II from Iceland., Methods: Genomic DNA was extracted from blood leukocytes of patients with MCD, their healthy family members, and from control individuals. CHST6 mutations were determined by PCR-sequencing. Immunophenotypes of MCD were determined by measuring antigenic keratan sulfate (AgKS) levels in serum and by an immunohistochemical study on corneal tissue., Results: Five additional cases of MCD type I and four families with MCD type II from Iceland were studied. A homozygous p.A128V mutation in the coding region of the CHST6 gene was identified in four of the five MCD type I cases. The other person with MCD type I was a compound heterozygote for p.A128V and a frameshift p.V6fs resulting from a 10-base pair insertion (c.15_16insATGCTGTGCG). Four of five individuals with MCD type II were compound heterozygotes for p.A128V and p.V329L, thus sharing the same p.A128V mutation as MCD type I. One patient with MCD type II was homozygous for p.V329L. The p.V329L mutation was only found in MCD type II patients. An analysis of the upstream region of CHST6 disclosed no upstream deletion or replacements in Icelandic patients with MCD type II., Conclusions: The findings fit the haplotype analysis that we reported previously in Icelandic MCD families and indicate that different mutations in CHST6 cause MCD type I and type II in Iceland.

Objective: To study whether Chinese patients with various corneal dystrophy carry mutations in BIGH3 gene., Methods: Genomic DNA was extracted from Chinese patients with Avellino corneal dystrophy (ACD, 10 cases), Reis-Bücklers corneal dystrophy (CDRB, 2 cases), granular corneal dystrophy (GCD, 3 cases) and 5 control subjects. The exons 4 and 12 of BIGH3 gene were amplified by PCR and the product was sequenced directly., Results: All 15 patients carried mutations in BIGH3 gene, R124H in 10 cases with ACD, R124L in 2 cases with CDRB and R555W in 3 cases with GCD., Conclusions: Corneal lesions in all 15 Chinese patients clinically diagnosed with corneal dystrophies are caused by mutations in BIGH3 gene. Dose-effect analysis shows that corneal lesions are more severe in homozygous patients than those in heterozygous cases and that clinical manifestation of patients with R124L mutation is more severe than that of patients with R124H mutation.