Clinical, Cytogenetic, and Biochemical Analyses of a Family with a t(3;13)(q26.2;p11.2): Further Delineation of 3q Duplication Syndrome.

Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies. Partial duplication of chromosome 3q syndrome is a well-described condition, and the phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation. Approximately 60%-75% of cases are derived from a balanced translocation. We describe a family with a pure typical partial trisomy 3q syndrome derived from a maternal balanced translocation t(3;13)(q26.2;p11.2). As the chromosomal rearrangement involves the short arm of an acrocentric chromosome, the phenotype corresponds to a pure trisomy 3q26.2-qter syndrome. There are 4 affected individuals and several carriers among three generations. The report of this family is relevant because there are few cases of pure duplication 3q syndrome reported, and the cases described here contribute to define the phenotype associated with the syndrome. Furthermore, we confirmed that the survival until adulthood is possible. This report also identified the presence of glycosaminoglycans in urine in this family, not related to the chromosomal abnormality or the phenotype.

A familial reciprocal translocation t(1;15) in three generations identified in a regular trisomy 21 patient.

The concurrence of a reciprocal translocation and an aneuploidy represent a rare coincidence and an interchromosome effect between these two events has been suggested. We report the case of a family with a t(1;15) in three generations which was identified through the evaluation ofa patient with classical trisomy 21 or Down syndrome. The cytogenetic analysis with GTG banding showed that the proband had a regular trisomy 21 and a balanced translocation t(1;15). FISH and microsatellite analysis were carried out in the family in order to discard an interchromosomal effect. The implications for genetic assessment are discussed.

Clinical delineation of a patient with trisomy 1q32.qter and monosomy 5p resulting from a familial translocation 1;5.

We describe a patient who had multiple malformations including ventriculomegaly, colpocephaly, corpus callosum, cerebellum and vermix hypoplasia, optic nerve hypoplasia, corneal opacity and congenital heart disease in whom a trisomy 1q32-qter and monosomy 5p derived from a t(1;5)mat was diagnosed by karyotype and FISH analysis. This trisomy/monosomy association has not been previously reported. The familial analysis of the translocation was carried out in four generations and its implications on the phenotype of the patient and genetic counseling are discussed.

PCR-PRINS-FISH analysis of structurally abnormal sex chromosomes in eight patients with Turner phenotype.

According to cytogenetic analysis, about 50% of Turner individuals are 45,X. The remaining cases have a structurally abnormal X chromosome or are mosaics with a second cell line containing a normal or abnormal sex chromosome. In these mosaics, approximately 20% have a sex marker chromosome whose identity cannot usually be determined by classical cytogenetic methods, requiring the use of molecular techniques. Polymerase chain reaction (PCR), primed in situ labeling (PRINS), and fluorescence in situ hybridization (FISH) analyses were performed in 8 patients with Turner syndrome and 45,X mosaic karyotypes to determine the origin and structure of the marker chromosome in the second cell line. Our data showed that markers were Y-derived in 2 patients and X-derived in the remaining 6 patients. We were also able to determine the breakpoints in the two Y chromosomes. The use of cytogenetic and molecular techniques allowed us to establish unequivocally the origin, X or Y, of the marker chromosomes in the 8 patients with Turner phenotype. This study illustrates the power of resolution and utility of combined cytogenetic and molecular approaches in some clinical cases.