Biomedical subjects
Publications and source records attributed to M R Krawczyński.
The authors present a classification of retinitis pigmentosa (rp) based on the modes of inheritance. Known genetic conditions of autosomal recessive, X-linked recessive and autosomal dominant forms of rp are shown, presenting molecular principles of the illness. They also describe clinical subtypes of rp with suggested genotype-phenotype correlations and principles of modern genetic diagnostics and genetic counselling.
Basic information about mitochondrial inheritance have been presented. The nature of inheritance of Leber's hereditary optic neuroretinopathy (LHON) has been described. The recent reports about heterogeneity of mutations, heteroplasm and nucleo-mitochondrial interaction have been taken into consideration. Principles of modern genetic diagnostics and counselling of LHON have been described.
A girl, 15, with Marshall syndrome, was hospitalized for retinal tear and detachment of the left eye. The results of ophthalmological examination and applied eye surgery have been described. The authors confirm the essential phenotypical overlap of Marshall and Stickler syndromes. This suggest that they are caused by variable expression of a differently mutated gene, probably the type II procollagen gene (COL2A1), known to play a part in the etiology of Stickler syndrome. This justifies the usage, by some authors, of the common name of Marshall-Stickler syndrome.
Normal human colour vision is based on the presence of 3 kinds of cones containing 3 different visual pigments, sensitive to short (blue), middle (green) and long (red) wavelengths. Congenital defects of colour vision are based on handicap or total loss of these pigments' function, usually a result of changes in their coding genes. The common types of colour blindness, referred to red-green axis, are present in about 8% of males and 0.44% of females. 3/4 of them are deuteranopes or deuteranomalous trichromats and 1/4 of them are protanopes or protanomalous trichromats. All of them are inherited in X-linked recessive way. The genes have been already mapped and sequenced. The cause of the great majority of their changes is nonhomologous recombination, which produces a gene deletion or creates the red-green or green-red hybrid genes. The result of that is the production of visual pigment with partly or totally changed spectral sensitivity.
Between the rare types of colour blindness, the known best are defects of blue colour vision, which are called tritanopia or trinanomaly (tritanomalous trichromacy). Their incidence is 1 in 500 and they are inherited in autosomal dominant way with incomplete penetrance. The basis of them are mutations of the short (blue) wavelength sensitive visual pigment gene. The gene has been mapped on the chromosome 7 and has already been cloned and sequenced. However, the loci heterogeneity should not be excluded in that condition. Another rare type of colour blindness in blue cone monochromacy. It is based on the cone sensitivity to short (blue) wavelength only. The condition is inherited in X-linked recessive way and it is known, that it can be caused by 2 different mechanisms. The first one--two-step pathway--consists of green cone pigment gene deletion, and point mutation of red cone pigment gene. The second one--one-step pathway--arose by deletion of regulatory sequence of both genes of visual pigments, mapped on the X chromosome. Different types of total and partial achromatopsia are also described. The best known ones are: rod monochromacy, which is inherited in autosomal recessive way and consist of rod vision only, and cone dystrophy, usually inherited in X-linked recessive way.
The modern view for the mechanisms of retinoblastoma origination, based on the tumor suppressor genes theory, has been described in this work. The structure and function of the retinoblastoma gene and its protein product, with reference to the cell cycle, has been presented. On the ground of this data, possibilities of genetic molecular diagnostics and principles of competent genetic counselling have been described.