Identification of three new mutations of the HNF-1 alpha gene in Japanese MODY families.

AIM/HYPOTHESIS: We analysed Japanese MODY patients for mutations in the HNF-1 alpha gene. METHODS: Fifty unrelated Japanese patients with early-onset diabetes (diagnosed at 25 years of age or younger) or with a strong family history of diabetes were screened for mutations in the HNF-1 alpha gene. Functional studies of the mutant HNF-1alpha were carried out. RESULTS: We identified three new mutations in the HNF-1 alpha gene in the families with a strong family history for diabetes. One mutation (L518P519fsTCC --> A) was identified in three unrelated families, while the other two mutations (T521I and V617I) were identified in one family. We also identified the A site of the promoter (+102G-to-C), which was reported previously. We examined the functional properties of the mutant HNF-1alpha. By increasing the amount of L518P519fsTCC-->A-HNF-1alpha, increasing inhibition of the transcription of human transthyretin (TTR) was observed (up to 61% of the control). Increasing amounts of T521I-HNF-1alpha or V617I-HNF-1alpha mutant proteins increased TTR promoter transcription up to 4.3-fold and 2.4-fold, respectively, whereas both increased transcription up to 12.4-fold of the control. CONCLUSION/INTERPRETATION: The L518P519fsTCC --> A was identified for the first time and this mutation might be a common cause of Japanese MODY3 in Okinawa area. In addition, both the T521I and V617I mutations were present in two patients in the same family. Since the prevalence of these mutations is relatively high (10%, 5/50), the HNF-1 alpha gene needs to be screened for mutations in patients either with early-onset diabetes or with a strong family history for diabetes.

Specular microscopic observation of posterior corneal vesicles.

Specular microscopic investigation was conducted on 5 cases with the diagnosis compatible with posterior corneal vesicles. Endothelial cells were considerably enlarged with a more or less indistinct margin. Deposits onto endothelial cells were occasionally seen. The results of specular microscopy suggest that posterior corneal vesicles be classified as a nonfamilial, unilateral variant of posterior polymorphous dystrophy of the cornea.

[Effects of photocoagulation on diabetic macular edema].

Retrospective analysis of clinical cases observed for three years with respect to the appearance of the fundus and visual acuity was conducted to evaluate the effect of photocoagulation therapy on macular edema in relation to whither diabetic retinopathy was accompanied by, focal or cystoid, macular edema. In addition to glycemic control, focal and direct treatment of responsible lesions was found effective for focal macular edema in simple diabetic retinopathy. Concerning all types of retinopathy, the prognosis of focal macular edema was significantly favorable to that of cystoid macular edema. Blood sugar control also influenced the prognosis of focal edema. The changes of retinopathy were closely associated with the prognosis of focal macular edema in preproliferative and proliferative retinopathy. Disseminated photocoagulation and panretinal photocoagulation showed no difference as to the results of indirect treatment of focal macular edema in preproliferative retinopathy. Macular alterations other than macular edema occurred in a higher proportion of cases of proliferative retinopathy than in simple or preproliferative retinopathy. This accounted for low visual recovery in the former group in comparison to simple retinopathy. It was concluded that the direct treatment of the involved lesions is effective for focal macular edema in simple retinopathy and that extensive photocoagulation in preproliferative and proliferative retinopathy indirectly has a favorable influence on focal edema by means of amelioration of retinopathy.