The Prader-Willi syndrome and the Angelman syndrome

The Prader-Willi syndrome and the Angelman syndrome are characterised by a complex clinical and behavioural phenotype resulting from loss of paternal or maternal expression, respectively, of genes located on the human chromosome 15q11-13. Different molecular mechanisms leading to this imbalance have been identified, including microdeletions, intragenic mutations, uniparental disomy and imprinting centre defects. Low copy repeat gene clusters are known to flank the 15q11-13 microdeletion. They predispose to unequal crossing-over events resulting in the deletion. Involvement of multiple disease genes is strongly suspected and traditional positional cloning techniques as well as animal models are used to identify the involved genes. In this review we include the present state of art and a delineation of future approach to study the candidate genes in these two syndromes.     

Kartagener's syndrome and the syndrome of immotile cilia

Summary Kartagener's syndrome (KS) is a hereditary disease with typical symptoms of situs inversus, bronchiectasis, and chronic infections of the nasal mucosa. Autosomal recessive inheritance cannot be doubted on account of repeated observations of affected sibs and parental cansanguinity. The bronchopulmonary symptoms in sibs, however, cannot be explained by this mode of inheritance.Recent clinical findings and electron microscope investigations suggest that KS is a special form of manifestation within the immotile cilia syndrome. This disease combines the typical bronchial and nasal symptoms of KS with sterility in the male due to immotile sperm tails and, as a facultative symptom, situs inversus. Thus, sibs with bronchiectasis but without situs inversus are also classified under this syndrome. The symptoms mentioned are caused by an abnormal morphology of bronchial cilia and sperm tails, which can be demonstrated by electron microscopy. The dynein arms normally attached to the nine microtubular doublets and providing a normal ciliary movement are lacking.It is assumed that during early embryonic life ciliary beats in the growing embryo determine the type of laterality. When ciliary movements are absent laterality may develop fortuitously, thus effecting a situs inversus in about half the affected cases. The numerical evaluation of pedigrees from the literature supports this assumption.