Pure 6p22-pter trisomic patient: Refined FISH characterization and genotype-phenotype correlation

First described in 1971, partial trisomy 6p is uncommon and generally secondary to a familial reciprocal translocation. The proximal breakpoint of the reported cases varies from p11 to p25. We here report on a patient with moderate mental retardation, craniofacial and pigmentary anomalies, proteinuria, and hyperglycemia who was found to have a mosaic karyotype 46,X,add (Y)(q12)/45,X. Fluorescence in situ hybridization (FISH) enabled us to identify that the additional material on Yqh derived from 6p and to define the rearrangement as der(Y)t(Y;6)(q12;p22). To the best of our knowledge, this is the first case of trisomy 6p22-pter without an associated deleted segment; the second breakpoint of the rearrangement is in Yqh. Precise mapping of the centromeric breakpoint of the trisomic 6p segment allowed a more convincing correlation between partial 6p trisomy and clinical phenotype to be addressed. In particular, the proteinuria often observed in 6p trisomic patients could be assigned to the 6p22-6pter region. (C) 2002 Wiley-Liss, Inc

Il cariotipo in pazienti con diagnosi clinica di sindrome di Down: Valutazione di un campione di 1588 soggetti.

A collaborative study between genetic centers in North East Italy was performed. Data on all subjects who underwent a citogenetic examination because of clinical suspect of Down syndrome from 1973 to 1985 were analyzed. All data regarding sex, age at clinical observation and karyotype are presented in table 1 . The incidente of trisomy 21 and other chromosomal abnormalities is 4, 5%. A mosaic was detected in 1.34 % of karyotype. All data are in agreement with the literature. The foilowing considerations can be obtained by data regarding karyotype/phenotype correlation, sex and age at clinical observation of the subjects: 1) the male/female ratio (1 . 24/1) significantly differs from that of normal population (p < 0 .025). The ratio does not change with the increasing of the subjects age. There is no a selection sex dur\uecng postnatal life ; 2) a higher proportion of female rather than male (p < 0 .001) with clinical diagnosis of Down syndrome have a normal karyotype. The Authors are not able to explain this latter observation

Cytogenetic and molecular evaluation of 241 small supernumerary marker chromosomes: cooperative study of 19 Italian laboratories

PURPOSE: We evaluated the experiences of 19 Italian laboratories concerning 241 small supernumerary marker chromosomes (sSMCs) with the aim of answering questions arising from their origin from any chromosome, their variable size and genetic content, and their impact on the carrier's phenotype. METHODS: Conventional protocols were used to set up the cultures and chromosome preparations. Both commercial and homemade probes were used for the fluorescent in situ hybridization analyses. RESULTS: A total of 113 of the 241 sSMCs were detected antenatally, and 128 were detected postnatally. There were 52 inherited and 172 de novo cases. Abnormal phenotype was present in 137 cases (57%), 38 of which were antenatally diagnosed. A mosaic condition was observed in 87 cases (36%). In terms of morphology, monocentric and dicentric bisatellited marker chromosomes were the most common, followed by monocentric rings and short-arm isochromosomes. The chromosomes generating the sSMCs were acrocentric in 132 cases (69%) and non-acrocentric chromosomes in 60 cases (31%); a neocentromere was hypothesized in three cases involving chromosomes 6, 8, and 15. CONCLUSION: The presented and published data still do not allow any definite conclusions to be drawn concerning karyotype-phenotype correlations. Only concerted efforts to characterize molecularly the sSMCs associated or not with a clinical phenotype can yield results suitable for addressing karyotype-phenotype correlations in support of genetic counseling

Cytogenetic and molecular evaluation of 241 small supernumerary marker chromosomes: Cooperative study of 19 Italian laboratories

PURPOSE: We evaluated the experiences of 19 Italian laboratories concerning 241 small supernumerary marker chromosomes (sSMCs) with the aim of answering questions arising from their origin from any chromosome, their variable size and genetic content, and their impact on the carrier's phenotype. METHODS: Conventional protocols were used to set up the cultures and chromosome preparations. Both commercial and homemade probes were used for the fluorescent in situ hybridization analyses. RESULTS: A total of 113 of the 241 sSMCs were detected antenatally, and 128 were detected postnatally. There were 52 inherited and 172 de novo cases. Abnormal phenotype was present in 137 cases (57%), 38 of which were antenatally diagnosed. A mosaic condition was observed in 87 cases (36%). In terms of morphology, monocentric and dicentric bisatellited marker chromosomes were the most common, followed by monocentric rings and short-arm isochromosomes. The chromosomes generating the sSMCs were acrocentric in 132 cases (69%) and non-acrocentric chromosomes in 60 cases (31%); a neocentromere was hypothesized in three cases involving chromosomes 6, 8, and 15. CONCLUSION: The presented and published data still do not allow any definite conclusions to be drawn concerning karyotype-phenotype correlations. Only concerted efforts to characterize molecularly the sSMCs associated or not with a clinical phenotype can yield results suitable for addressing karyotype-phenotype correlations in support of genetic counseling

De novo balanced chromosome rearrangements in prenatal diagnosis

none50GIARDINO D; CORTI C; BALLARATI L; COLOMBO D; SALA E; VILLA N; PIOMBO G; PIERLUIGI M; FARAVELLI F; GUERNERI S; D. COVIELLO; LALATTA F; CAVALLARI U; BELLOTTI D; BARLATI S; CROCI G; FRANCHI F; SAVIN E; NOCERA G; AMICO FP; GRANATA P; CASALONE R; NUTINI L; LISI E; TORRICELLI F; GIUSSANI U; FACCHINETTI B; GUANTI G; DI GIACOMO M; SUSCA FP; PECILE V; ROMITTI L; CARDARELLI L; RACALBUTO E; POLICE MA; CHIODO F; RODESCHINI O; FALCONE P; DONTI E; GRIMOLDI MG; MARTINOLI E; STIOUI S; CAUFIN D; LAURICELLA SA; TANZARIELLO SA; VOGLINO G; LENZINI E; BESOZZI M; LARIZZA L; DALPRÀ LGiardino, D; Corti, C; Ballarati, L; Colombo, D; Sala, E; Villa, N; Piombo, G; Pierluigi, M; Faravelli, F; Guerneri, S; Coviello, Domenico; Lalatta, F; Cavallari, U; Bellotti, D; Barlati, S; Croci, G; Franchi, F; Savin, E; Nocera, G; Amico, Fp; Granata, P; Casalone, R; Nutini, L; Lisi, E; Torricelli, F; Giussani, U; Facchinetti, B; Guanti, G; DI GIACOMO, M; Susca, Fp; Pecile, V; Romitti, L; Cardarelli, L; Racalbuto, E; Police, Ma; Chiodo, F; Rodeschini, O; Falcone, P; Donti, E; Grimoldi, Mg; Martinoli, E; Stioui, S; Caufin, D; Lauricella, Sa; Tanzariello, Sa; Voglino, G; Lenzini, E; Besozzi, M; Larizza, L; Dalprà, L

De novo balanced chromosome rearrangements in prenatal diagnosis

OBJECTIVE: We surveyed the datasheets of 29 laboratories concerning prenatal diagnosis of de novo apparently balanced chromosome rearrangements to assess the involvement of specific chromosomes, the breakpoints distribution and the impact on the pregnancy outcome. METHOD: By means of a questionnaire, data on 269.371 analyses performed from 1983 to 2006 on amniotic fluid, chorionic villus and fetal blood samples were collected. RESULTS: A total of 246 balanced anomalies were detected at frequencies of 72% for reciprocal translocations, 18% for Robertsonian translocations, 7% for inversions and 3% for complex chromosome rearrangements. The total frequencies of balanced rearrangements were 0.09%, 0.08% and 0.05% on amniotic fluid, chorionic villus and fetal blood samples. CONCLUSION: A preferential involvement of chromosomes 22, 7, 21, 3, 9 and 11 and a less involvement of chromosomes X, 19, 12, 6 and 1 was observed. A nonrandom distribution of the breakpoints across chromosomes was noticed. Association in the location of recurrent breakpoints and fragile sites was observed for chromosomes 11, 7, 10 and 22, while it was not recorded for chromosome 3. The rate of pregnancy termination was about 20%, with frequencies decreasing from complex chromosomal rearrangements (33%), reciprocal translocations (24%) to inversions (11%) and Robertsonian translocations (3%