ABSTRACT
Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three chains (alpha 3, beta 3, and gamma 2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been established as the genetic basis for the inherited blistering skin disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the alpha 3 chain gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a premature termination codon (CGA-->TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysis was used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10 weeks' gestation in a subsequent pregnancy. The fetus was predicted to be genotypically normal with respect to the LAMA3 mutation.
Subject(s)
Cell Adhesion Molecules/genetics , Epidermolysis Bullosa, Junctional/genetics , Point Mutation , Base Sequence , Child , Chorionic Villi Sampling , DNA Mutational Analysis , DNA Primers , Female , Homozygote , Humans , Macromolecular Substances , Male , Molecular Sequence Data , Pedigree , Polymerase Chain Reaction , Pregnancy , Prenatal Diagnosis , KalininABSTRACT
OBJECTIVE: To determine whether there is a reduction in human forearm skin capillary density in essential hypertension. SUBJECTS AND METHODS: We compared the number of capillary loops in the forearm skin of 12 patients with established, uncomplicated essential hypertension (mean blood pressure 180/109 mmHg) with that in carefully matched control subjects, using intravital capillaroscopy and fluorescein angiography. RESULTS: There was a significant reduction in forearm skin capillary density in the hypertensive patients compared with the normotensive subjects. This represents a reduction by approximately 20% in capillary density. Capillary density was inversely correlated with blood pressure in the hypertensive patients alone (r = -0.4, P < 0.05) and in the whole group. CONCLUSION: The present study demonstrates a reduction in capillary density in the forearm of patients with essential hypertension. If this rarefaction in the forearm is also present in other vascular beds, it could result in an approximately 20% increase in peripheral resistance, which might play an important additional role in determining blood pressure.
