Trisomy 3 (p23-pter) resulting from maternal translocation, t (3 ; 4)(p23 ; q35).

We describe a patient with partial trisomy 3p resulting from maternal translocation, t(3:4)(p23;q35). The male newborn who died at the age of 22 hours presented with distinct facial features including a square-shaped face with prominent forehead and depressed temporal regions, prominent cheeks, short broad nose, left cleft lip and cleft palate, malformed ears, and a receding mandible. Further findings were flexion deformities of the fingers with finger-like thumbs and mild cutaneous syndactyly 2/3 and 4/5, hypoplastic penis and scrotum with no palpable testes. He probably had a congenital heart defect and situs inversus abdominalis. Many of these features have been reported in other patients with distal trisomy 3p.     

Closing in on the BPES gene on 3q23: mapping of a de Novo reciprocal translocation t(3;4)(q23;p15.2) breakpoint within a 45-kb cosmid and mapping of three candidate genes, RBP1, RBP2, and beta'-COP, distal to the breakpoint

BPES is a genetic disorder presenting with blepharophimosis, ptosis of the eyelids, epicanthus inversus, and telecanthus. BPES type I is associated with female infertility, whereas type II presents without additional symptoms. Hitherto, it remains unknown whether BPES type I results from a defect in a single gene or from a contiguous gene syndrome. Previous cytogenetic and linkage analyses have assigned a BPES locus to 3q23, in a 5-cM interval between D3S1615 and D3S1316. In this report, we describe the molecular and physical characterization of the 3q23 breakpoint in a BPES patient with a t(3;4)(q23;p15.2) translocation. Eight YACs located around and within the D3S1615-D3S1316 interval were mapped relative to the 3q23 breakpoint; 5 YACs spanning the 3q23 breakpoint were identified. Thirteen STSs and ESTs were localized on the YAC map. Subsequent hybridization of 2 YACs spanning the breakpoint to the Human RPCI1 PAC Library and the Human Chromosome 3 LLNL Cosmid Library resulted in the identification of 12 PACs and 50 cosmids respectively, allowing the construction of a detailed PAC and cosmid physical map. A refined position-telomeric to the breakpoint-of 3 candidate genes, cellular retinol-binding proteins 1 and 2 (RBP1, RBP2) and the coatomer beta' subunit (beta'-COP), was obtained on this physical map. Furthermore, a PAC and cosmid contig encompassing the breakpoint was constructed. PAC 169-C 10 and cosmid 11-L 10 crossing the breakpoint have sizes of 110 and 45 kb, respectively. The isolation of coding sequences in these clones and in the rest of the contig will greatly facilitate further efforts toward positional cloning of the gene(s) involved in BPES.     

Partial trisomy 4q: Two cases with a familial translocation t(4;18)(q27;q23)

Clinical and cytogenetic data of two related patients, both trisomic for the segment 4q27 to qter, are reported. Familial studies determined that the mothers of the two probands were carriers of the same balanced translocation between chromosomes 4 and 18. Altogether, two partial trisomies 4q, five balanced karyotypes, and one 45,X0 karyotype were found in the family. The 18 cases reported to date are reviewed with respect to the karyotype-phenotype correlation.     

Translocation between chromosome 7 and chromosome 22, t(7;22)(p22;q12), in a patient with chronic myelocytic leukemia

Summary A 46-year-old man with chronic myelocytic leukemia had a new variant translocation between chromosome 22 and chromosome 7 in bone marrow cells. No involvement of chromosome 9 was seen. The patient entered blastic transformation within half a year, by which time he had acquired an isochromosome 17 in addition to the variant translocation.     

4p- syndrome in a girl with translocation t(1;4)(q11;p16)mat

Summary A newborn girl had features of the 4p- syndrome. Cytogenetic studies of the mother showed a translocation t(1;4)(q11;p16). The proband had the translocation, but the band 4p16 had been lost.     

Balanced familial translocation t(5;19)(q12;p or q11) with phenotypical abnormalities in a girl.

Human diploid fibroblasts cultured in Dulbecco's Modified Eagle's medium (DME) were exposed to different concentrations of 15 antibiotics to determine the limiting toxic concentration. The number of cells surviving after antibiotic treatment was given as the index of toxicity. No visible chromosomal damage could be detected when half the maximal toxic concentration was applied. The maximum limiting concentration was found to be the same for both the preconfluent and postconfluent phases.     

A Palindrome-Mediated Recurrent Translocation with 3:1 Meiotic Nondisjunction: The t(8;22)(q24.13;q11.21)

Palindrome-mediated genomic instability has been associated with chromosomal translocations, including the recurrent t(11;22)(q23;q11). We report a syndrome characterized by extremity anomalies, mild dysmorphia, and intellectual impairment caused by 3:1 meiotic segregation of a previously unrecognized recurrent palindrome-mediated rearrangement, the t(8;22)(q24.13;q11.21). There are at least ten prior reports of this translocation, and nearly identical PATRR8 and PATRR22 breakpoints were validated in several of these published cases. PCR analysis of sperm DNA from healthy males indicates that the t(8;22) arises de novo during gametogenesis in some, but not all, individuals. Furthermore, demonstration that de novo PATRR8-to-PATRR11 translocations occur in sperm suggests that palindrome-mediated translocation is a universal mechanism producing chromosomal rearrangements.     

Analysis of segregation and aneuploidy in two reciprocal translocation carriers, t(3;9)(q26.2;q32) and t(3;9)(p25;q32), by triple-color fluorescence in situ hybridization

Meiotic segregation patterns of chromosomes 3 and 9 were analyzed in sperm of two translocation carriers (t(3;9)(q26.2;q32) and t(3;9)(p25;q32)) by triple-color fluorescent in situ hybridization (FISH) with a telomeric DNA probe in addition to two centromeric probes. The frequencies of each sperm product resulting from alternate or adjacent I, adjacent II and 3:1 segregation in a t(3;9)(q26.2;q32) translocation carrier were 88.35%, 5.44% and 5.94%, respectively. On the other hand, the frequencies of each sperm product in a t(3;9)(p25;q32) translocation carrier were 89.23%, 6.02% and 4.48%, respectively. Of all the sperm products, the frequency of normal or chromosomally balanced sperm in a t(3;9)(q26.2;q32) and a t(3;9)(p25;q32) were 52.49% and 47.25%, respectively. The frequencies of each sperm product resulting from various segregations were different between both carriers and significantly deviated from the expected frequencies. Additional dual-color and triple-color FISH were performed to analyze aneuploidy rates for chromosomes 12, 17, 18, X and Y in order to detect any interchromosomal effect; no evidence of an interchromosomal effect was found.     

Novel translocation t(3;11)(p21;q24) in multiple myeloma characterised by FISH

We present a 72 year old man with multiple myeloma (MM). Cytogenetic and FISH analysis of bone marrow aspirate showed a novel translocation -der(11)t(3;11)(p21;q24). The unbalanced karyotype led to substantial partial trisomy for chromosome 3p and small partial monosomy 11q. Structural rearrangements of chromosome 3 are uncommon in MM and these are reviewed. The patient died 2 years after the diagnosis of MM was made.     

A de novo 3p13 deletion induced by a complex chromosomal rearrangement combined with a pericentric inversion of chromosome,inv(3)(p13q12), and a translocation between chromosome 3 and 8, t(3;8)(q13.1;q24.2), in a child with developmental delay

A de novo complex chromosomal rearrangement is very rare but likely to be present in a child with developmental disabilities and physical alterations. A child presented in this study showed global developmental delay and some typical phenotypes. Initial karyotyping and FISH analysis in the patient showed an apparently de novo balanced translocation between chromosome 3 and 8, t(3;8)(q13.1;q24.2). Further analysis using multiplex ligation-dependent probe amplification and array-based comparative genomic hybridization revealed a cryptic microdeletion on 3p13 region. Nearly one-third of balanced rearrangements are reported to involve cryptic disruptions at breakpoints, however, the microdeletion of the proposita was present in non-translocated region of the chromosome 3. After careful reevaluation of the results, a pericentric inversion, inv(3)(p13q13.1) that induced deletion was revealed. The clinical features of developmental delay in cognition, language, and motor function and facial and physical phenotype of the proposita were similar to those found in the children with 3p13 deletion. This case shows that combined molecular cytogenetic techniques with routine karyotyping are very useful to identify subtle genomic changes associated with abnormal phenotypes.     

11q Aneuploidy: Partial monosomy and trisomy in the children of a mother with a t(3;11)(p27;q23) translocation

Summary A woman with a balanced translocation t(3;11)(p27;q23) has had three abnormal children. The first child died in infancy, and of the two survivors who show segregation of the derivative maternal translocated chromosomes, one exhibits partial trisomy 11q and the other partial monosomy 11q. The two cases are compared with each other and with reported examples. Moreover, 11q break points are discussed.     

Translocation 46,X, t(Y;7)(q122;q11) in a case of male sterility]

A Y-autosome translocation--46,X,t(Y;7)(q122;q111)--in a steril man is reported and compared with others already reported in the literature.     

2 cases of partial trisomy 10p due to a paternal translocation t(10p;18)(p13;q23)]

Two brothers trisomic for the distal two thirds of 10p are reported. Trisomy results from the malsegregation of a familial translocation rcp (10;18)(p13;q23) present in the father, a half-brother and the grand-father of the propositi. The phenotype is comparable to that of other 10p trisomic patients reported in the literature.     

Partial trisomy 4q: Two cases resulting from a familial translocation t(4;18)(q27;p11)

Summary Partial trisomy of the long arm of chromosome 4 was observed in two related patients, a child aged 2 years and a woman aged 42. Cytogenetic investigation revealed that their chromosome anomalies were due to segregation of a familial balanced translocation t(4;18)(q27;p11). Some clinical and cytogenetic considerations are noted.     

Pure 4p trisomy due to a de novo 4q;22p dicentric translocated chromosome karyotype 46,XX,-22,+t(4;22)(q1200;p13).

A de novo t(4;22)(q1200;p13) is reported in a girl with a florid 4p trisomy phenotype. The abnormal chromosome was identified by high resolution, C-bands and confirmed by 5-BrdU as de novo dicentric translocated chromosome.     

A dysmorphic newborn with 45,X,der(1)inv(1)(p13;qter)t(Y;1)(pter-->q11;p13),-Y de novo karyotype

A dysmorphic newborn with 45,x,der(1)inv(1)(p13;qter)t(y;1)(pter-->q11;p13),-Y de novo karyotype: Y/autosome translocations are very rare chromosomal rearrangements. In most cases, the long arm of the Y chromosome is translocated onto an autosome and most patients are referred because of male infertility. Y/1 translocations are very rare, and have been reported in seven patients so far. Pericentric inversions may be seen in all chromosomes and are not associated with phenotypic abnormalities. Here we report a 6-day old male baby with prenatal growth retardation, frontal bossing, hypertelorism, micrognathia, cleft soft palate, absent uvula, hypospadias, simian line in both hands and hammer toes. Cytogenetic analysis was performed with GTG-banding, C-banding and FISH analysis containing X centromeric probe, Yq12-qter locus specific probe and whole chromosome Y probe. An unbalanced Y/1 translocation was diagnosed: 45,X,der(1)inv(1)(p13;qter)t(Y;1)(pter-->q11;p13),-Y.