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Instability of the centromeric region of chromosome 1 and multibranched configurations formed by different numbers and combinations of arms of chromosomes 1, 9, and 16 were found in cultured lymphocytes of a 12-year-old male with combined IgA and IgE deficiency. No chromosome abnormalities were found in fibroblast cultures from the patient or in blood cultures from his parents. A possible effect on the frequency of the abnormalities of the almost continuous antibiotic treatment received by the patient was found both in vivo and in vitro, but no abnormalities were found in blood cultures from control subjects who received similar treatment. Interphase association of chromosomes 1, 9, and 16 and a high frequency of interchanges among the centromeric regions of these chromosomes due to the presence of a fragile site is assumed to be the cause of the abnormalities.

Backgroundterminal deletions of the distal portion of the short arm of chromosome 3 cause a rare contiguous gene disorder characterized by growth retardation, developmental delay, mental retardation, dysmorphisms, microcephaly and ptosis. The phenotype of individuals with deletions varies from normal to severe. It was suggested that a 1,5 Mb minimal terminal deletion including the two genes CRBN and CNTN4 is sufficient to cause the syndrome.In addition the CHL1 gene, mapping at 3p26.3 distally to CRBN and CNTN4, was proposed as candidate gene for a non specific mental retardation because of its high level of expression in the brain.Methods and Resultswe describe two affected siblings in which array-CGH analysis disclosed an identical discontinuous terminal 3p26.3 deletion spanning less than 1 Mb. The deletion was transmitted from their normal father and included only the CHL1 gene. The two brothers present microcephaly, light mental retardation, learning and language difficulties but not the typical phenotype manifestations described in 3p- syndrome.Conclusiona terminal 3p26.3 deletion including only the CHL1 gene is a very rare finding previously reported only in one family. The phenotype of the affected individuals in the two families is very similar and the deletion has been inherited from an apparently normal parent. As already described for others recurrent syndromes with variable phenotype, these findings are challenging in genetic counselling because of an evident variable penetrance.

Five females with duplication of the short arm of one chromosome 9 are reported, one tetrasomic and four trisomic for 9p. The tetrasomy is due to an isochromosome 9p while the trisomies are due in one case to an intrachromosomal duplication present in lymphocytes but not in fibroblasts, two are secondary to translocations with chromosomes 22 and 13 respectively, and one is a mosaic with a cell line with an additional deleted chromosome 9 present in lymphocytes and fibroblasts. This analysis indicates that duplications 9p may result in impairment of ovarian function. The phenotypic differences between trisomy and tetrasomy 9p are discussed.

Cytogenetic investigations for diagnostic purposes were performed on 1000 first trimester samples of chorionic villi (CVS) in two laboratories using similar techniques. Fetal karyotyping was the primary indication for CVS in 912 and maternal age was the major indication in 758 of them. The risk category "previous child/fetus with chromosome abnormality" included 74 diagnoses, while the category "chromosome abnormality in one of the parents" included 38 diagnoses. Sex determination was the primary indication for CVS in 53 pregnancies. The overall incidence of chromosomal abnormalities was 70, of which 47 were balanced and 23 unbalanced. The results are detailed for each of the risk categories and the incidence of abnormal karyotypes is given for each year of maternal age. In the maternal age of 35-37 years the incidence of unbalanced karyotypes was 2.9% and in the years 38 onwards it was 6.6%. The incidence of unbalanced karyotypes was about 4% when the sampling was made in the weeks 9 to 12 but six abnormal karyotypes were found among 39 CVS performed at the eight week of gestation. The 11 trisomies of the type not found at birth were clustered between the 8th and the 10th week of pregnancy. The technical problems encountered in this experience and the preliminary estimates of fetal loss are discussed.