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The molecular characterisation of chromosomal aberrations in Xp22

A young male with a karyotype of 46, X,+mar is described. Physical mapping of the marker chromosome by using Y-specific single-copy or moderately repeated DNA sequences as molecular probes showed that, in addition to the heterochromatic part of the Yq, a considerable portion of the euchromatin in both Yp and Yq had been lost. These findings suggest that the marker chromosome is a ring Y, for the generally accepted model of ring formation implies breakages in both chromosome arms. The clinical features of the patient correlated well with the phenotypic changes expected from the loss of genetic material from the Y.

Molecular genetic analysis of the transmission of mutations in 73 families with fragile X (one of the largest samples evaluated so far) has confirmed previous hypotheses that the fragile X syndrome results from two consecutive mutational steps, designated "premutation" and "full fragile X mutation". These mutations give rise to expansions of restriction fragments, most probably by amplification of the FMR-1 CGG repeat. Premutations are identified by small expansions that apparently have no effect on either the clinical or the cellular phenotype. Full mutations are reflected by large expansions and hypermethylation of the expanded gene region. All males showing large expansions were affected. Individuals with full mutations also expressed the fragile X, with only one exception. An affected "mosaic" male, showing a predominance of premutated fragments in his leukocytes, was shown to be fragile-X-negative on different occasions. About 50% of heterozygotes with full mutations were reported by clinicians to be mentally retarded. Conversion of the premutation to the full mutation may occur at oogenesis, as previously suggested, or after formation of a zygote at an early transitional stage in development when the CGG repeat behaves as a mitotically unstable element on maternally derived/imprinted X chromosomes carrying a premutation of sufficient repeat length.

The activity of plasma creatine kinase activity was investigated in Swiss albino mice, in mice with hereditary muscular dystrophy (strain 129) and their heterozygote littermates. In affected mice enzyme activity was markedly elevated (2 to 10 times the normal mean). No difference was noted between the enzyme activity of mice aged 6 and 10 weeks. Heterozygotes had the same plasma enzyme activities as Swiss albino mice. It is suggested that hereditary dystrophy in mice is more similar to the limb girdle type of human muscular dystrophy in respect to plasma enzyme changes. This would be in agreement with the cause of the disease, which in both instances is an autosomal recessive gene.

A mild bleeding tendency with characteristics of the von Willebrand disease was documented in family members of a girl with glycogen storage disease type Ib (GSD) Ib). It was assumed that a defective glucose-6-phosphate dependent microsomal glycoprotein synthesis was involved in the bleeding disorder of the patient and the GSD Ib heterozygotes.

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Die Gesamtaktivltt der alkalischen Serumphosphatase stellt die Summe von Einzelaktivitäten mehrerer organspeziftscher Isoenzyme dar. Bei allen gesunden Erwachsenen lassen sich im Blutserum mit der Acrylamidelektrophorese die beiden aus der Leber und dem Knochen stammenden Isoenzyme nachweisen. Bei etwa 40-50% der Erwachsenen tritt außerdem ein aus dem Dünndarm stammendes Isoenzym auf (3).Bei unklar erhöhten Werten der alkalischen Serumphosphatase ermöglicht die elektrophoretische Isoenzymdifferenzlerung zunächst eine Unterscheidung von Leber-und Knochenkrankheiten. Die quantitative Messung der so getrennten Isoenzyme kann vor allem zu einer Differenzierung der Leberkrankheiten beitragen.