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Pitt-Hopkins syndrome (PHS) is a probably underdiagnosed, syndromic mental retardation disorder, marked by hyperventilation episodes and characteristic dysmorphism (large beaked nose, wide mouth, fleshy lips, and clubbed fingertips). PHS was shown to be caused by de novo heterozygous mutations of the TCF4 gene, located in 18q21. We selected for this study 30 unrelated patients whose phenotype overlapped PHS but which had been initially addressed for Angelman, Mowat-Wilson, or Rett syndromes. In 10 patients we identified nine novel mutations (four large cryptic deletions, including one in mosaic, and five small deletions), and a recurrent one. reported, most of which either consist in deletion of significant portions of the TCF4 coding sequence, or generate premature stop codons. No obvious departure was observed between the patients harboring point mutations and large deletions at the 18q21 locus, further supporting TCF4 haploinsufficiency as the molecular mechanism underling PHS. In this report, we also further specify the phenotypic spectrum of PHS, enlarged to behavior, with aim to increase the rate and specificity of PHS diagnosis.

In vitro models are required for the study of these cancers, and several cell lines have already been established and characterised (Lafargues & Ozzello, 1958;Soule et al., 1973;Cailleau et al., 1974;Engel et al., 1978;Whitehead et al., 1983;Yamane et al., 1984;Chu et al., 1985;Vandewalle et al., 1987). Nevertheless, owing to the heterogenity and the diversity of mammary cancers, a great number of cell models is necessary to understand the reasons for this diversity and the effect of anticancer drugs on tumour cells.Cytogenetic studies of mammary adenocarcinoma cell lines are essential for comprehension of the pathogenesis of these cancers (Trent, 1985;Gebhart et al., 1986). The implication of chromosomal alterations in these pathologies has opened a new and promising route towards better knowledge of these cancers (Cervenka & Koulischer, 1973). Chromosomal alterations are generally numerous, and markers often demonstrate hyperploidy in these cancers (Sandberg, 1980). Demonstration of the minimum genetic alterations indispensable for cell transformation is difficult, and might be easier on cells with a karyotype closer to normal. Sandberg and Wolman mentioned the existence of such cells, but most of their results concerned karyotype studies without chromosome banding (Sandberg, 1980;Wolman, 1983 [-', hyaluronidase 25 IU for 20 ml, Hepes buffer 4.8 g 1' in distilled water). Cells were then fixed in acetic acid:methanol (1:3) and dropped onto grease-free, cooled slides for chromosome counting and examination. R bands were obtained by heat denaturation of the chromosomes according to the method of Dutrillaux and Lejeune (1971). Xenografted CAL51 cells were plated and studied in vitro in the same manner.

Congenital microphthalmia is a common developmental ocular disorder characterized by shortened axial length. Isolated microphthalmia is clinically and genetically heterogeneous and may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Here, we studied a five-generation family of Sephardic Jewish origin that included 38 members, of whom 7 have either unilateral or bilateral microphthalmia of variable severity inherited as an autosomal dominant trait with incomplete penetrance. After exclusion of several candidate loci, we performed a genome-scan study and demonstrated linkage to chromosome 15q12-q15. Positive LOD scores were obtained with a maximum at the D15S1007 locus (maximum LOD score 3.77, at recombination fraction 0.00). Haplotype analyses supported the location of the disease-causing gene in a 13.8-cM interval between loci D15S1002 and D15S1040.

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