Tetrasomy 5p mosaicism due to an additional isochromosome 5p in a man with normal phenotype

Tetrasomy 5p mosaicism due to a supernumerary isochromosome for the short arm of chromosome 5 is a rare constitutional cytogenetic aberration described in only four postnatally ascertained patients to date [Sijmons et al., 1993; Stanley et al., 1993; LordaS anchez et al., 1997b; Hansen et al., 2003]. The clinical findings overlap the pattern delineated in patients with complete and partial trisomy 5p affecting at least band 5p13 [Lorda-S anchez et al., 1997a] and include: macrocephaly, facial anomalies, short neck, club feet, abdominal muscles hypoplasia, heart defects, feeding and respiratory difficulties and anomalies of the central nervous system with dilated cerebral ventricles and hydrocephaly as main complication. Generalized hypotonia with seizures and psychomotor retardation can be also present. In two patients pigmentary dysplasia was reported [Stanley et al., 1993; Hansen et al., 2003]. The differences between patients are presumed to be due to the percentage of cells with i(5p) and tissue distribution of the mosaicism [Sijmons et al., 1993]. We present a 35-year-old Caucasian man with normal phenotype and a de novo 47,XY,þi(5p)[8]/46,XY[42] mosaicism observed only in peripheral blood lymphocytes but not in skin fibroblasts and urothelial cells. He was referred with his wife to our Reproductive Medicine Unit because of 5 years infertility and two miscarriages in the first trimester of gestation. The couple had a healthy 8-year-old female. The patient had a normal stature (184 cm) and examination showed no dysmorphic facial features or minor anomalies. Hematochemical and hemocytometric analyses were normal and echocardiographic examination and electrocardiographic monitoring did not show evidence of congenital heart defects. No respiratory difficulties, hypotonia or seizure episodes were reported. Sperm analysis and count did not show significant alterations of the parameters measured. The patient’s family history was unremarkable. To investigate the possible causes of our patient’s infertility and recurrent miscarriages, chromosome analysis was performed on 50 Q-banded metaphases from the peripheral blood lymphocytes. In eight cells a supernumerary marker chromosome, suggestive of an isochromosome of the short arm of chromosome 5, was observed and the karyotype defined as 47,XY,þi(5)(p10)[8]/ 46,XY[42]. The finding was confirmed in a second blood sample. FISH analysis with a locus specific identifier probe which hybridizes to the 5p15.2 locus (D5S23, D5S271, LAVysion, Abbott Molecular, Abbott Park, IL) confirmed the nature of the marker chromosome (Fig. 1) and the observation of 1,100 nuclei demonstrated the presence of the i(5p) in almost the same percentage ascertained on metaphases (13.3%). Parental karyotypes performed on blood lymphocytes turned to be normal, but in the father we observed a greater percentage of chromosomal breakage and rearrangements (41.0%) compared to our laboratory standard (7.6%). He did not report any kind of exposure to mutagens. Cytogenetic analysis was then performed on skin fibroblasts: chromosome analysis showed a normal karyotype in 100 metaphases observed and FISH, performed on 1,000 nuclei with the LSI 5p15.2 probe, did not show evidence of the marker. We decided to investigate another tissue without using invasive techniques and FISH analysis was then performed on 200 urothelial cells obtained from voided urine. No evidence of the isochromosome was ascertained. During the patient’s management, his 37-year-old wife got pregnant and a prenatal genetic diagnosis on amniotic fluid was offered at 15þ4 weeks of gestation, also because of maternal age. No evident fetal ultrasound abnormalities were observed at the