Breakpoint within the nucleolus organizer region resulting in a reciprocal translocation t (4;14)(q21;p12)

Reciprocal translocations involving a break in the nucleolus organizer region (NOR) are rare. A balanced translocation in a mother and her fetus with breakpoints in the NOR at 14p12 and on the long arm of a chromosome 4 at band 4q21 is described. The rearrangement was characterized by Ag-NOR staining, multiplex fluorescence in situ hybridization (M-FISH), and FISH with rDNA probes. This and other cases with breakpoints within NORs are discussed.     

Tandem duplication of nucleolus organizer region (NOR) in the Japanese macaque, Macaca fuscata fuscata

During exploration of chromosome polymorphisms in Japanese macaques, a heteromorphic polymorphism was found in a population in the Zigokudani monkey park. The population consisted of three troops (social units). Of 36 monkeys examined, five females showed heterozygotic 'marker' chromosome (chromosome 9). The polymorphism was a tandem duplication of the nucleolus organizer region (NOR) of the short arm of chromosome 9, which was found for the first time in the genus Macaca. FISH and fibre-FISH using human 18S rDNA and sequential silver nitrate staining revealed that the duplicated region included a part of the euchromatic satellite and the stalk and that the euchromatic block (intercalary satellite) divided the NOR into two parts (distal and proximal). Furthermore, it showed that the distal region possessed much more rDNA than the proximal region, and that the duplications might have been introduced via a mechanism of gene amplification (inverted duplications associated with over-replication and recombination events). As the tandem duplication was observed sporadically in four maternal pedigrees in two troops and the mothers of the variants all had normal chromosomes, the variation might have been introduced from another population's gene pool by a solitary male immigrant.     

Rubinstein‐Taybi syndrome caused by a de novo reciprocal translocation t(2;16)(q36.3;p13.3)

Rubinstein‐Taybi syndrome (RTS) is a multiple congenital anomalies and mental retardation syndrome characterized by facial abnormalities, broad thumbs, and broad big toes. We have shown previously that disruption of the human CREB‐binding protein (CBP) gene, either by gross chromosomal rearrangements or by point mutations, leads to RTS. Translocations and inversions involving chromosome band 16p13.3 form the minority of CBP mutations, whereas microdeletions occur more frequently (∼10%). Breakpoints of six translocations and inversions in RTS patients described thus far were found clustered in a 13‐kb intronic region at the 5′ end of the CBP gene and could theoretically only result in proteins containing the extreme N‐terminal region of CBP. In contrast, in one patient with a translocation t(2;16)(q36.3;p13.3) we show by using fiber FISH and Southern blot analysis that the chromosome 16 breakpoint lies about 100 kb downstream of this breakpoint cluster. In this patient, Western blot analysis of extracts prepared from lymphoblasts showed both a normal and an abnormal shorter protein lacking the C‐terminal domain, indicating expression of both the normal and the mutant allele. The results suggest that the loss of C‐terminal domains of CBP is sufficient to cause RTS. Furthermore, these data indicate the potential utility of Western blot analysis as an inexpensive and fast approach for screening RTS mutations. Am. J. Med. Genet. 92:47–52, 2000. © 2000 Wiley‐Liss, Inc.     

Familial t(6;21)(p21.1;p13) translocation associated with male-only sterility

A 38-year-old male with primary infertility was referred for cytogenetic investigation. Karyotype analysis revealed a 46,XY,t(6;21)(p21.1;pl3) translocation. The Ag-nucleolar organizer regions (NORs) banding technique demonstrated that the 21p NORs were retained in the derivative and actively transcribed. Family studies showed that three brothers, two sisters and their mother carried the t(6;21). All carrier males suffered from primary infertility with severe oligoasthenoteratospermia or azoospermia, whereas at least two of the three carrier women were fertile. The region of the translocation breakpoint was narrowed down cytogenetically and by fluorescence in situ hybridisation as 21p13 and 6p21.1. Southern blot analysis showed that the gene ZNF165, which maps to this region and which is specifically expressed in the testis, was not disrupted by the translocation. However, studies performed on testicular biopsy showed spermatocyte meiosis anomalies. We discuss the possible mechanisms by which the translocation might affect meiosis in spermatogenesis and lead to infertility.     

Meiotic segregation in familial reciprocal translocation t(8q;22q)

We studied the chromosomes of a mentally retarded boy with minor anomalies and of his parents using a G-band stained high-resolution chromosome method. This documented dup (8q24.1 → 8qter) and dup(22pter → 22q11.2) in the boy due to a maternal balanced reciprocal translocation of chromosomes 8 and 22 and 3:1 disjunction during meiosis I. The karyotype of the boy is 47, XY, + der(22) (22pter → 22q11.2::8q24.1 → 8qter). The der(22) was involved in satellite associations and stained positively with AgNO₃ in mother and child. The case is compared to similar cases in the literature and the function of the small acrocentric marker chromosome during meiosis is discussed.     

Congenital arhinia with de novo reciprocal translocation, t(3;12)(q13.2;p11.2)

A female newborn suffering from congenital arhinia with complete airway obstruction is reported. In addition, she had hypertelorism, microphthalmia, high-arched palate, and hypoplasia of the auditory canal and mastoid and facial bones, along with the absence of olfactory bulbs and tracts. She had a de novo reciprocal translocation between chromosomes 3q13.2 and 12p11.2. Certain gene(s) located at either of the breakpoints, 3q13.2 and 12p11.2, may be involved in the pathogenesis of her arhinia.     

Derivative (14)t(11;14)(q13;q32)t(11;14)(p11.2;p11.2): a novel unbalanced variant of the t(11;14)(q13;q32) translocation in mantle cell lymphoma

We report the case of a 62-year-old man who presented with splenomegaly, leukocytosis, anemia, and thrombocytopenia. Examination of the peripheral blood, bone marrow, and spleen revealed involvement by mantle cell lymphoma, with some blastoid features and an atypical phenotype. Spleen and bone marrow classical chromosome analysis followed by fluorescence in situ hybridization revealed a novel and unusual unbalanced variant of the t(11;14)(q13;q32) translocation, resulting in a complex derivative chromosome harboring the IGH/CCND1 fusion gene. This chromosome was designated as der(14)t(11;14)(q13;q32)t(11;14)(p11.1;p11.2).     

Familial reciprocal translocation, t(2;10)(p24;q26), resulting in duplication 2p and deletion 10q

We describe a familial reciprocal translocation between the distal part of the short arm of chromosome 2 and the long arm of chromosome 10. Five individuals in two generations had multiple congenital anomalies. Their karyotypes were 46, XX or XY,−10, + der(10), t(2;10)(p24;q26). Seven persons were balanced translocation carriers whose karyotypes were 46, XX or XY, t(2;10)(p24;q26). Common manifestations included mental retardation, strabismus, narrow high-arched palate, wide alveolar ridges, other facial abnormalities, genital abnormalities and mutism. The phenotype of the unbalanced individuals is compared to that of previously published cases of the syndrome of partial duplication 2p and to reported patients with partial deletion of 10q.     

Polymorphism of the nucleolus organizer region (NOR) on the putative sex chromosomes of Arctic char (Salvelinus alpinus) is not sex related

Polymorphism of the nucleolus organizer region (NOR) on the putative sex chromosomes of Arctic char (Salvelinus alpinus) was examined using conventional cytogenetic and molecular techniques. Variation was observed in the number, size and position of rDNA loci on the sex pair. Fluorescence in situ hybridization (FISH) analyses showed that the sex chromosomes of Arctic char lack the repetitive DNA sequences (MboI/BglII family) that are a prominent feature of the sex chromosomes of lake trout (S. namaycush). Southern analyses of genomic DNAs using an rDNA fragment as probe revealed extensive restriction fragment length polymorphism (RFLP) variation among individuals. Despite the presence of variation in all aspects of this rDNA locus, no sex-specific differences were detected. Repetitive DNAs (multicopy rDNA as in Arctic char or tandem repetitive DNA as in lake trout) appear to play important but different roles in the evolution of the sex chromosomes in these species.This revised version was published online in November 2005 with corrections to the Cover Date.     

Sperm FISH studies in seven male carriers of Robertsonian translocation t(13;14)(q10;q10)

BACKGROUND: Robertsonian translocation t(13;14) is one of the most common structural reorganization in humans, but meiotic segregation studies in these carriers are still limited. The segregation pattern of the chromosomes involved, the possible influence of the translocated chromosomes on the synapsis and disjunction of other chromosome pairs [interchromosomal effects (ICE)] and the rates of unbalanced spermatozoa produced still deserve attention, not only to obtain a better characterization of the meiotic behaviour of this reorganization, but also to offer carrier couples accurate genetic counselling. METHODS: Multicolour fluorescence in-situ hybridization was used to analyse the segregation of chromosomes 13 and 14 and the possible occurrence of ICE (on chromosomes 18, 21, 22, X and Y) in seven male carriers of a t(13;14)(q10;q10). RESULTS AND CONCLUSIONS: The individuals analysed showed a homogeneous segregation pattern, with a clear predominance of alternate segregations resulting in the production of normal/balanced spermatozoa (83-88.23%). A significant increase in the disomy rates for the sex chromosomes, which could be considered as a positive ICE, was observed in two of the carriers analysed.     

Translocation t(X;21)(q13.3; p11.1) in a girl with Menkes disease

A girl with a 46,X,t(X;21) (q13.3;p11.1) karyotype presented with skin redundancy, especially in the neck, prominent occiput and micrognathia, and later developed hypotonia, hypopigmentation, sparse scalp hair, and profound mental retardation characteristic of Menkes disease. Her serum copper (14 μg/dl) and ceruloplasmin (9 mg/dl) levels were extremely low. Fluorescent in situ hybridization analysis with a 100-kb P1-derived artificial chromosome probe containing the Menkes disease gene demonstrated three twin-signals, one on the normal X chromosome and one each on derivative chromosomes X and 21, indicating that the Xq13.3 breakpoint was located within the gene. Replication pattern analysis showed that the normal X chromosome was late replicating, whereas the derivative X chromosome was selectively early replicating. These results indicated that Menkes disease in our patient resulted from a de novo translocation that disrupts the disease gene. Am. J. Med. Genet. 79:191–194, 1998. © 1998 Wiley-Liss, Inc.     

Paternal Robertsonian translocation t(13q;14q) and maternal reciprocal translocation t(7p;13q) in a couple with repeated fetal loss.

Marriages involving partners both of whom have abnormal karyotypes are rare and are usually ascertained because of a history of infertility, repeated abortions, or the birth of a balanced translocation carrier or chromosomally abnormal offspring. Abnormalities which have been noted include sex chromosome aberrations in both parents or a sex chromosome abnormality in one parent and an autosomal abnormality in the other. Four papers have reported balanced reciprocal autosomal translocations in both parents, two couples representing a first cousin marriage. We present a case of a paternal 13;14 Robertsonian translocation and a maternal (7p;13q) reciprocal translocation in a couple with repeated fetal loss.     

A reciprocal t(4;9)(q31;p22) in a solitary neurofibroma

Cytogenetic reports of solitary neurofibromas are rare and, to our knowledge, no clonal reciprocal translocations have been reported in these tumors. Reciprocal chromosome translocations have been identified in a number of solid tumors and can have both diagnostic and prognostic significance. We report the first case of a solitary circumscribed neurofibroma with a (4;9)(q31;p22) balanced reciprocal translocation as the sole cytogenetic abnormality.     

Fluorescencein situ hybridization with rDNA probes on chromosomes of two nucleolus organizer region phenotypes of a species ofEigenmannia (Pisces,Gymnotoidei, Sternopygidae)

Nucleolus organizer regions (NORs) were analysed in two related and geographically close populations ofEigenmannia sp. 1 (Pisces, Gymnotoidei, Sternopygidae) using silver staining and fluorescencein situ hybridization (FISH). The two populations differed in their Ag-NOR phenotypes, displaying fixed differences in the NOR-bearing chromosome pairs. FISH with rDNA probes showed that these differences were due to the location of rDNA cistrons. This finding, showing fixed NOR differences between two populations belonging to the same species in a connected river system, is highly significant in terms of evolutionary change, possibly indicating an initial step of genetic differentiation. This result also has important implications from the cytosystematic point of view, as NORs usually have a very constant karyotypic location in fish species and have been used as species-specific chromosome markers.accepted for publication by M. Schmid     

Translocation (1;19)(q21;q13.3) is a recurrent reciprocal translocation in meningioma

Benign meningiomas are characterized by a normal karyotype or loss of all or part of chromosome 22. Histologically higher grade tumors are typically characterized by a pattern of increasing chromosome loss and instability. This characteristic pattern of unbalanced chromosome aberrations is punctuated in the literature by several intriguing reports of a reciprocal t(1;19)(q21;q13.3) as the sole cytogenetic aberration. We report a third case showing the t(1;19)(q21;q13.3) with additional unstable secondary aberrations of a dic(18;22)(p11;p11) and telomeric fusions.     

Congenital diaphragmatic hernia in a family segregating a reciprocal translocation t(5;15)(p15.3;q24)

Congenital diaphragmatic hernia (CDH) is a relatively common malformation of unknown cause with high mortality due to hypoplasia of the lungs and pulmonary hypertension. We studied a family in which two fetuses had CDH, and two pregnancies resulted in first trimester missed abortions. Both fetuses with CDH had an apparently normal karyotype. In a subsequent pregnancy, fluorescent in situ hybridization analysis of amniocytes showed a balanced translocation 46,XY, t(5;15) (p15.3;q24) also present in the mother and in a normal child, suggesting that the diaphragmatic hernia in the first two fetuses was caused by a cryptic unbalanced translocation. This hypothesis is supported by a previous observation of CDH in a distal deletion of 15q as part of a multiple congenital anomalies syndrome. It is suggested that a gene distal to 15q21 is important for the normal development of the diaphragm.