Meiotic consequences of an intrachromosomal insertion of chromosome No. 1: a family pedigree

In three generations of the proband's patrilineal relatives, 14 subjects were found to be carriers of a "shift" insertional chromosome No. 1 (46XX or XY, ins(1)(p32q25q31)). The proband and three female relatives, who were mild to moderate mental retardates with minor congenital anomalies, were trisomic for the insertional segment, (1)q25q31. Another subject, who was a markedly immature female abortus with congenital abnormalities, was found to be monosomic for this same chromosomal segment. The cytogenetic evidence suggests that each of these unbalanced recombinant progeny was the result of a single crossing over in the noninsertional loop of a paternal pachytene bivalent of the balanced insertional chromosome No. 1.     

Partial trisomy 19p: case report and natural history

Partial trisomy 19p was noted in an infant delivered at 39 weeks gestation with intrauterine growth retardation (IUGR), bilateral club feet, renal abnormalities, hearing deficit, and multiple dysmorphic features. Chromosomes obtained following amniocentesis at 32 weeks gestation revealed that the fetus was partially trisomic for 19p and partially monosomic for a portion of the terminal band of 3q, having inherited a derivative chromosome 3 from her father [46,XX,-3,+der(3)t(3;19)(q29;p13.2)pat]. The father was found to be the carrier of a balanced translocation between chromosomes 3 and 19 [46,XY,t(3;19)(q29;p13.2)]. The only other case of partial trisomy 19p previously reported was an infant with partial trisomy 19p and partial monosomy 13q who died at 59 days of age. This report by Byrne et al. [(Am J Hum Genet 1980: 32:64A] is similar to our case with respect to IUGR, small palpebral fissures, and ear anomalies.     

Three cases of partial trisomy 9q in one generation due to maternal reciprocal t(6;8;9) translocation

A family is described in which three siblings had congenital abnormalities consistent with partial trisomy 9q syndrome. Karyotyping indicated that the mother was a carrier of two separate balanced reciprocal translocations involving three chromosomes (46,XX,t (6;8;9)(6q27;8p23;9q32;9q13] resulting from four breakpoints. The three siblings had inherited the der(8) from their mother and hence were partially trisomic for 9q32----9qter and partially monosomic for 8p23----8pter (46,XX,der(8),t(8;9)(p23;q32)mat). The clinical features of the three cases were comparable to those reported in the literature.     

Retinoblastoma,deletion 13q14, and esterase D: Application of gene dosage effect to prenatal diagnosis

Esterase D (ESD) gene dosage studies were performed on amniotic cells from a fetus at risk for del 13q14. The mother was a balanced carrier of an insertion in chromosome #20: 46,XX,ins(20;13)(p12;q1307q14.3). She had already given birth to a monosomic child with retinoblastoma (Rb) and to a phenotypically normal child trisomic for the same 13q14 segment. Both sibs displayed the expected proportionate gene dosage effects for ESD. A 153% value of ESD activity was found in the amniotic cells indicating unambiguously that the fetus was not monosomic for segment 13q14 and therefore not at increased risk for Rb. The mother delivered a phenotypically normal child who was confirmed to be trisomic for segment 13q14 by cytogenetic analysis and by gene dosage studies for ESD in cord blood cells and in lymphoblastoid cells.     

Translocation 1;7 in preleukemic states

A translocation t(1;7) interpreted as t(1;7)(p11;p11) was first reported by Scheres et al. in eight patients with various hematologic disorders. The karyotype of the abnormal cells was trisomic for 1q and monosomic for 7q. Those investigators reported having found four other cases in the literature. We report herein studies of two patients with the same t(1;7).     

Molecular characterisation of partial chromosome 21 aneuploidies by fluorescent PCR

Although trisomy of chromosome 21 is the most prevalent human genetic disorder, data from partial 21 aneuploidies are very scanty. Eight different partial aneuploidies for chromosome 21 were characterised by fluorescence quantitative PCR. Allelic dosage analysis was performed for each patient using 25 CHLC STRs covering the entire q arm. The length of the corresponding trisomies and monosomies was ascertained for five partial trisomics and three partial monosomics. All trisomic patients carried unbalanced translocations involving chromosome 21, whereas one of the monosomic patients bore a ring chromosome 21 and another showed an interstitial deletion of chromosome 21. The chromosomal breakpoints of two partial trisomy patients could be clearly delimited. However, the other three trisomies involved most of the 21 q arm as three allelic doses were detected for each marker. Although these latter patients do not show all the features of Down syndrome, genotype/phenotype correlations agree with previously reported data. The chromosomal breakpoints observed in two partially monosomic patients helped further to define the region involved in different phenotypic features associated with chromosome 21 monosomy. Telomeric material loss was also detected in a patient bearing a ring 21 chromosome. The parental origin of the aneuploidy was assigned for each case, which allowed us to conclude that two of the monosomic cases originated from de novo chromosomal rearrangements. There was no correlation with parental sex in contrast to trisomic patients originating from meiotic nondisjunction.     

Trisomy 1q24----1q41 in two sibs with an insertion in an inverted chromosome 4.

We report two patients whose karyotype revealed an additional segment 1q inserted into an inverted chromosome 4. The patients were partially trisomic for the region 1q24----1q41, karyotype 46,XY or XX, inv ins(4;1)inv(4)(q28;q24q41)(p15 . 3q28), while in the mother the chromosomal aberration was balanced. The inserted segment was inverted. In six patients from three other families with insertions, the segment 1q25----1q32 was inserted into the short arm of chromosome 1. In another patient, the segment 1q25----1q42 of the mother was inverted and inserted into the long arm of chromosome 6. These findings suggest an increased susceptibility for a segment of the long arm of chromosome 1 to be inserted and inverted in rearrangements.     

Familial balanced insertion (5;10) and monosomy and trisomy (10) (q24.2→q25.3)

The phenotype of a boy with monosomy of a small segment of chromosome (10) (q24.2----q25.3) is described. In his family a balanced insertion (5;10) is found in three generations. Moreover there are two persons who are trisomic for the same small segment of chromosome 10 for which the boy is monosomic.     

Segregation of an insertional chromosome rearrangement in 3 generations.

The interstitial deletion of a segment of chromosome 13, 13q21 leads to 13q22, and its inversion and insertion into the long arm of chromosome 3 at breakpoint q12, was found to segregate in 3 generations of a family. Segregation of this 3 break rearrangement gave rise to individuals monosomic, trisomic, or balanced for the involved segment. Monosomy for 13q21 leads to 13q22 was associated with mental retardation, expressive aphasia, microcephaly, hand abnormalities, and short stature. Partially trisomic individuals had normal mentality, extremely high arched palate, and mild dysmorphic features. There was no evidence for retinoblastoma in the individuals examined. The balanced carriers were normal. Comparison of monosomic individuals with one previous report of a similar deletion reveals marked phenotypic similarities.     

The phenotypic effects of chromosome rearrangement involving bands 7q21.3 and 22q13.3.

We report a family in which the proband has a direct insertion of band 7q21.3 into chromosome 22 at 22q13.3, karyotype 46,XX,dir ins(22;7)(q13.3;q21.2q22.1). Two of her children have unbalanced chromosome rearrangements involving 7q21.3, with one girl monosomic for the region and a boy trisomic for the region. The child monosomic for band 7q21.3 has a split hand/split foot (SHSF) anomaly and her clinical features are consistent with the 7q21-q22 contiguous gene deletion syndrome. In situ hybridisation studies have shown that the proband and her son have a submicroscopic deletion of chromosome band 22q13.3. Interstitial deletions of this chromosome band have rarely been reported.     

Trisomy 3p23----pter and monosomy 11q23----qter in an infant with two translocation carrier parents.

A newborn male infant with multiple congenital abnormalities was found to be trisomic for 3p23----pter and monosomic for 11q23----qter. His parents were both carriers of a balanced reciprocal translocation. Considerable overlap in phenotype-karyotype correlations was found between the two chromosomal syndromes in the patient.     

Mirror-symmetric duplicated chromosome 21q with minor proximal deletion, and with neocentromere in a child without the classical Down syndrome phenotype

We report on a mentally retarded child with multiple minor anomalies and an unusually rearranged chromosome 21. This der(21) chromosome has a deletion of 21p and of proximal 21q, whereas the main portion of 21q is duplicated leading to a mirror-symmetric appearance with the mirror axis at the breakpoint. The centromere is only characterized by a secondary constriction (with a centromeric index of a G chromosome) at an unexpected distal position, but fluorescence in situ hybridization (FISH) with either chromosome specific or with all human centromeres alpha satellite DNA shows no cross hybridization. Thus, the marker chromosome represents a further example of an "analphoid marker with neocentromere." Molecular analysis using polymorphic markers on chromosome 21 verified a very small monosomic segment of the proximal long arm of chromosome 21, and additionally trisomy of the remaining distal segment. Although trisomic for almost the entire 21q arm, our patient shows no classical Down syndrome phenotype, but only a few minor anomalies found in trisomy 21 and in monosomy of proximal 21q, respectively.     

Cryptic subtelomeric translocations in the 22q13 deletion syndrome

Cryptic subtelomeric rearrangements are suspected to underlie a substantial portion of terminal chromosomal deletions. We have previously described two children, one with an unbalanced subtelomeric rearrangement resulting in deletion of 22q13→qter and duplication of 1qter, and a second with an apparently simple 22q13→qter deletion. We have examined two additional patients with deletions of 22q13→qter. In one of the new patients presented here, clinical findings were suggestive of the 22q13 deletion syndrome and FISH for 22qter was requested. Chromosome studies suggested an abnormality involving the telomere of one 22q (46,XX,?add(22)(q13.3)). FISH using Oncor D22S39 and Vysis ARSA probes confirmed a terminal deletion. A multi-telomere FISH assay showed a signal from 19qter on the deleted chromosome 22. Results were confirmed with 19qtel and 22qtel specific probes. The patient is therefore trisomic for 19qter and monosomic for 22qter. The patient''s mother was found to have a translocation (19;22)(q13.42;q13.31). We also re-examined chromosomes from two patients previously diagnosed with 22q deletions who were not known to have a rearrangement using the multi-telomere assay. One of these patients was found to have a derivative chromosome 22 (der(22)t(6;22)(p25;q13)). No evidence of rearrangement was detected in the other patient. Thus we have found the 22q13 deletion to be associated with a translocation in three of four patients. This report illustrates the usefulness of examining patients with hypotonia, severe language delay, and mild facial dysmorphism for this syndrome and suggests that most of these deletions may be unbalanced subtelomeric rearrangements.     

Trisomy 20q caused by der(4) t(4;20) (q35;q13.1): report of a new patient and review of the literature

An infant with multiple congenital anomalies and severe developmental delay was found to have a derivative chromosome 4 by routine karyotypic analysis. Using telomeric FISH analysis, the source of the additional chromatin was determined to be from 20q. The infant, thus, is trisomic for 20q13.1 to 20qter and monosomic for the sub-telomeric region of 4q. Other cases of trisomy 20q13.1to 20qter associated with telomeric deletions are reviewed and compared to the current patient.     

Translocation 9q/13q resulting in duplication (trisomy 9pter→9q22) and deficiency (monosomy 13pter→13q12)

A profoundly retarded, 12-year-old female is described. Her phenotype is compatible with the clinical features of the trisomy 9p syndrome. Cytogenetic analyses showed her to be trisomic for 9pter→9q22 and monosomic for 13pter→13q12, as the result of adjacent-2 segregation during meiosis in her mother. The family pedigree shows this (9;13) translocation to be present in at least three generations.     

Histiocytic lymphoma cell lines: immunologic and cytogenetic studies

Cell lines were established from 15 patients with diffuse histiocytic lymphoma (DHL) of the intermediate grade, diffuse large cell (class G), and high-grade, large cell immunoblastic (class H) types. Immunologic studies indicated that 11 of the 15 DHL cell lines were B cell in origin, 2 were histiocytic, and 2 were null cell. Cytogenetic studies revealed 1 hypodiploid, 11 hyperdiploid, and 3 near-tetraploid cell lines. Chromosome #7 was trisomic in 3 lines, chromosomes #12 in 4 lines, and chromosome #13 in 3 lines. Chromosome #2 was monosomic in 3 lines, chromosome #8 was monosomic in 5 lines, chromosome #14 in 4 lines, and chromosome #22 in 6 cell lines. This is of special interest, as chromosomes #2, #8, #14, and #22 are clearly concerned with rearrangements in Burkitt's lymphoma and immunoglobulin expression. The most common rearrangement in the DHL cell lines involved chromosome #14 at band 14q32. However, in contrast to Burkitt's lymphoma, the pattern of translocation in DHL is between chromosome #14 and usually chromosome #11 or chromosome #18. The 14;18 translocation is not restricted to patients with low-grade follicular, small cleaved cell lymphomas, as has been reported. The 14q+ chromosome is characteristic of lymphoid malignancies in general. It is due, invariably, to a translocation with the breakpoint in band 14q32, which is the locus of the immunoglobulin heavy chain genes. We propose that in each translocation, for example, chromosomes #11 or #18, an oncogene may be transposed onto chromosome #14, and that each 14q+ translocation in DHL represents an event that transposes an oncogene from another chromosome to chromosome #14.     

Axenfeld-Rieger anomaly, hypertelorism, clinodactyly, and cardiac anomalies in sibs with an unbalanced translocation der(6)t(6;8)

We describe two sibs with the unbalanced translocation der(6)t(6;8)(p25.1;q24.23), making them monosomic for 6p25.1-->6pter and trisomic for 8q24.23-->8qter. The siblings both possess Axenfeld-Rieger Anomaly (ARA), hypertelorism, clinodactyly, and cardiac anomalies, but otherwise vary in the phenotypic manifestations of this unbalanced translocation. We compare them to previously described cases and a recently proposed syndrome of ARA, atrial septal defect, and sensorineural deafness.     

Axenfeld‐Rieger anomaly,hypertelorism, clinodactyly,and cardiac anomalies in sibs with an unbalanced translocation der(6)t(6;8)

We describe two sibs with the unbalanced translocation der(6)t(6;8)(p25.1;q24.23), making them monosomic for 6p25.1→6pter and trisomic for 8q24.23→8qter. The siblings both possess Axenfeld‐Rieger Anomaly (ARA), hypertelorism, clinodactyly, and cardiac anomalies, but otherwise vary in the phenotypic manifestations of this unbalanced translocation. We compare them to previously described cases and a recently proposed syndrome of ARA, atrial septal defect, and sensorineural deafness. © 2001 Wiley‐Liss, Inc.     

Mirror‐symmetric duplicated chromosome 21q with minor proximal deletion,and with neocentromere in a child without the classical Down syndrome phenotype

We report on a mentally retarded child with multiple minor anomalies and an unusually rearranged chromosome 21. This der(21) chromosome has a deletion of 21p and of proximal 21q, whereas the main portion of 21q is duplicated leading to a mirror‐symmetric appearance with the mirror axis at the breakpoint. The centromere is only characterized by a secondary constriction (with a centromeric index of a G chromosome) at an unexpected distal position, but fluorescence in situ hybridization (FISH) with either chromosome specific or with all human centromeres alpha satellite DNA shows no cross hybridization. Thus, the marker chromosome represents a further example of an “analphoid marker with neocentromere.” Molecular analysis using polymorphic markers on chromosome 21 verified a very small monosomic segment of the proximal long arm of chromosome 21, and additionally trisomy of the remaining distal segment. Although trisomic for almost the entire 21q arm, our patient shows no classical Down syndrome phenotype, but only a few minor anomalies found in trisomy 21 and in monosomy of proximal 21q, respectively. Am. J. Med. Genet. 91:116–122, 2000. © 2000 Wiley‐Liss, Inc.     

Effective monosomy or trisomy of chromosome band 2q37.3 due to the unbalanced segregation of a 2;11 translocation

We report a seven generation family in which a 2;11 chromosome translocation is segregating. Both unbalanced segregants have been found in the family, and cytogenetic analysis demonstrates that this results in effective monosomy or trisomy for chromosome band 2q37.3. Those family members who are monosomic exhibit a variable phenotype with a number of features associated with an Albright's Hereditary Osteodystrophy-like phenotype (AHO-like) whilst those who are trisomic have a phenotypic spectrum ranging from mild facial anomalies and growth retardation to apparent normality. The latter group of patients represent the first reported patients with pure trisomy for chromosome band 2q37.3.