Sex reversal due to Xp disomy by t(X;Y)(p21;q11).

A 20-month-old infant exhibiting psychomotor retardation, dysmorphisms and ambiguous external genitalia was found to have a 46-chromosome karyotype including a normal X chromosome and a marker Y with most of Yq being replaced by an extra Xp21-->pter segment. The paternal karyotype (G and C bands) was 46,XY. The marker Y composition was verified by means of FISH with a chromosome X painting, an alphoid repeat and a DMD probe. Thus, the final diagnosis was 46,X,der(Y)t(X;Y)(p21;q11)de novo.ish der(Y)(wcpX+,DYZ3+,DMD+). The patient's phenotype is consistent with the spectrum documented in 13 patients with similar Xp duplications in whom sex reversal with female or ambiguous genitalia has occurred in spite of an intact Yp or SRY gene. A review of t(X;Y) identifies five distinct exchanges described two or more times: t(X;Y)(p21;q11), t(X;Y)(p22;p11), t(X;Y)(p22;q11-12), t(X;Y) (q22;q12), and t(X;Y)(q28;q12). These translocations probably result from a recombination secondary to DNA homologies within misaligned sex chromosomes in the paternal germline with the derivatives segregating at anaphase I.     

Duplication 16q12----qter arising from 3:1 segregation in a 46,XX,t(13;16) (q12;q12) mother

A congenitally abnormal female baby was found to have the karyotype 46, XX, +der (16) t (13; 16) (q12;q12) mat. GTG, QFQ, CBG, THA and Ag-NOR banding techniques allowed the identification of the abnormal chromosomes in the proposita and in the translocation carriers through three generations. Duplication 16q resulted from 3:1 segregation in the carrier mother. The hypothesis of a specific meiotic segregation for this translocation is discussed. The phenotypic effects of proximal 16q duplications are analysed together with other four reported cases, which have similar duplicated segment and no other relevant chromosomal abnormality.     

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.     

Meiotic segregation analysis by FISH investigation of spermatozoa of a 46,Y,der(X),t(X;Y)(qter-->p22::q11-->qter) carrier

Chromosome analysis performed on a 30-year-old man revealed a 46,Y,der(X),t(X;Y)(qter-->p22::q11-->qter) karyotype, confirmed by fluorescence in situ hybridization (FISH). The man was of short stature, and no mental retardation was noticed; genitalia and testes were normal, as were the patient's FSH, LH, and testosterone blood levels. Sperm analysis showed azoospermia at the time of the first sampling and severe oligozoospermia, with 125,000 spermatozoa/milliliter, at the time of the second sampling. The sperm gonosomal complement of this patient and of a 46,XY donor were analyzed using multicolor FISH with X- and Y-chromosome probes. Our results clearly indicated that germinal cells carrying the translocation are able to complete the meiotic process by producing spermatozoa compatible with normal embryonic development, with more than 80% of the spermatozoa having either a Y chromosome or a der(X); however, a high level of spermatozoa with gonosomal disomies was observed. We also found a significant increase in the frequency of autosomal disomies in the carrier, which would suggest an interchromosomal effect. All previously reported cases in adult males were associated with azoospermia; testicular histological studies, performed in patients carrying the same X;Y translocation, showed spermatogenetic arrest after pachytene. To our knowledge, this is the first molecular analysis of the gonosomal complement in spermatozoa of men with a t(X;Y)(qter-->p22::q11-->qter).     

Translocation 11q;22q: a clinico-cytogenetic study]

Seven families with translocations t(11; 22) identified at our Institute and analysis of the literature showed that the imbalance resulted from such translocations is always due to nondisjunction 3:1. Nondisjunction occurs more often in the 1st meiotic division, and is more rare in the second one. Expressed prezygotic selection against spermia with an additional chromosome greatly increases the risk of having an imbalanced child for the women-carriers as compared to men-carriers. The phenotype of the patients with +der(22)t(11; 22) is composed of the features characteristic for trisomy 22q (cleft lip and palate, preauricular papillomas and fistulas, rectal atresia or stenosis) and trisomy 11q (long philtrum with the upper lip hanging over, renal al; asia and hypoplasia). Diaphragmatic hernias are found to be common for the patients with +der(22)t(11; 22).     

Mitotic and meiotic analysis of a reciprocal translocation t(Y;3) in an azoospermic male

Summary A balanced reciprocal translocation t(Y;3)(q11.2;q12) is detected in an azoospermic male, with a normal phenotype. Replication study shows no modification of the replication pattern of the bands of the rearranged chromosomes. Meiotic studies show a chain element at diakinesis. At the pachytene stage, the Y-body is in external contact with the sex vesicle. It is concluded that the integrity of the Y-chromosome is probably necessary for a normal meiotic process, and is more important than dosage effect due to complete or partial disomy of this chromosome.     

Meiotic chromosome segregation in human t(11;22)(q23;q11) carriers: a theoretical consideration

The t(11;22)(q23;q11) translocation is the most frequently encountered familial reciprocal translocation in humans. In the majority of reported cases ascertainment has been through the birth of a child with the chromosomal constitution 47,XX,+der(22) or 47,XY,+der(22), i.e., tertiary trisomy. Previous segregation analysis of familial cases showed a number of interesting features. Thus, euploid unbalanced genotypes resulting from adjacent segregation are absent in the progeny, and only tertiary trisomic offspring are recovered. To explain this unusual progeny output we present here a model for the meiotic behavior of this translocation in the carriers based on an analysis of cytogenetic data of progeny of carriers. This model predicts the formation of a chain trivalent with chromosome order 11-der(11)-22 during prophase I and its predominant alternate orientation at metaphase I.     

Familial translocation t(10;21)(q22;q22)

Summary A family is described with a translocation t(10;21)(q22;q22) transmitted through three generations. This family was studied for the apparition of several miscarriages and two sisters with multiple malformations. Both children had a probably partial trisomy of chromosome 10 and a monosomy of chromosome 21 due to a maternal adjacent-2 meiotic segregation.     

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.     

A prevalent Y;15 translocation in the Ethiopian Beta Israel community in Israel

We describe 7 cases of abnormal karyotypes involving chromosomes Y and 15 in Ethiopian Beta Israel patients: 46,XX, der(15)t(Y;15)(q12;p12) and 46,XY,der(15)t(Y;15)(q12;p12). Six cases were incidentally found in amniocentesis performed for various indications; the indication for karyotyping in 1 case was recurrent abortions. To the best of our knowledge, this is the first report of this translocation in a specific ethnic group. We conclude that the derivative chromosome 15 with chromosome Y is probably a normal variant in Ethiopian Beta Israel occurring at an estimated frequency of 4/74 (5.4%). The prenatal diagnosis of this translocation in this population probably does not require further parental testing.     

The phenotype in partial 13q trisomies,apropos of a familial (13;15)(q22;q26) translocation

Summary A 12 month-old male patient with a karyotype 46, XY,-15,+der(15),t(13;15)(q22;q26)pat is presented. His stillborn sib showed malformations compatible with the 13q deletion syndrome, probably due to a 46,XY, der(13) karyotype. Phenotypic analysis of 41 cases from the literature with partial distal 13q (D13q) trisomies indicate that the segment 13q22 qter in trisomy with or without another concomitant aneusomy is sufficient to produce the majority of the trisomy 13 syndrome features, some of which (cleft palate, increased HbF and projections in PMN) are present in different non-overlapping partial 13q trisomies. About 82% of the D13q trisomies are inherited, more frequently from the mother.     

Studies on chiasma frequency and distribution in two fertile men carrying reciprocal translocations; one with a t(9;10) karyotype and one with a t(Y;10) karyotype

Summary The frequency and distribution of chiasmata was investigated in two fertile carriers of reciprocal translocations, one with a 46,XY,t(9;10)(p22;q24) karyotype and one with a 46,X,-Y,+der(Y),t(Y;10)(q12;q24) karyotype. In both cases the chromosomes involved in the translocation showed an increase in chiasma frequency in comparison to karyotypically normal controls and in both cases this increase was localised, affecting only one interstitial segment of each translocation quadrivalent. In the t(9;10) case chiasmata appeared in substantial numbers in a novel location, the proximal two thirds of 9p, while in the t(Y;10) case chiasmata appeared in a conventional location, the medial region of 10q, but at an increased frequency. Furthermore there was evidence for inter-chromosomal effects in the t(9;10) case.     

SNP analysis of minimally evolved t(14;18)(q32;q21)-positive follicular lymphomas reveals a common copy-neutral loss of heterozygosity pattern

Follicular lymphoma (FL) cases with a t(14;18)(q32;q21) and minimal or no additional karyotypic alterations, such as copy number gains and losses and/or chromosomal rearrangements, may exhibit pathologic features and a clinical behavior similar to those with more complex karyotypes. This study sought to investigate whether the copy-neutral loss of heterozygosity (cnLOH) profiles of these minimally evolved t(14;18)(q32;q21)-positive follicular lymphoma (MEV-FL) cases are similar to or different from the majority of FL cases with more karyotypic alterations. Affymetrix SNP 6.0 array analysis was applied to the tumor genomes of 23 MEV-FL biopsy samples to assess for the presence of cnLOH. These cases carried either a single or no chromosomal abnormality in addition to t(14;18)(q32;q21) as determined by karyotyping. We found that, although these MEV-FL cases had simple karyotypes, they showed very similar cnLOH profiles as compared to cytogenetically complex cases. The most frequent regions affected by cnLOH were 1p (17%), 6p (17%), 12q (13%) and 16p (13%). Our study suggests that cnLOH alterations may serve as important contributors to the pathological and clinical manifestations of FL.     

47,XY,+der(11;22)(q23;q12) following balanced translocation t(11;22)(q23;q12)mat

Summary Report of a supernumerary extra chromosome der(11;22)(q23; q12) resulting from a balanced translocation in the mother. The propositus suffers from mental deficiency, deafness and extreme muscular weakness and exhibits cleft palate, a labial lymphangioma and an atrial septum defect. Since the features of partial trisomy 11q23 frequently associated with a translocation t(11q;22q) bear similarities with the cases of so called trisomy 22 one might conjecture that some of these observations are in fact products of translocations including partial 11q.     

Study of inter- and intra-individual variation of meiotic segregation patterns in t(3;15)(q27;q13) boars

Constitutional chromosomal rearrangements are relatively frequent genetic anomalies in both man and pigs. Among them, reciprocal translocations, present a specific meiotic segregation pattern. The potential "individual" effect of the t(3;15)(q27,q13) translocation was studied using SpermFISH to analyze the meiotic segregation patterns of three boars carrying this rearrangement. Three samples were taken at different times from one of these boars to analyze a potential "time" effect. No "time" or "individual" effect was found in this study. These results should allow more efficient management of certain reciprocal translocations in pig populations but need to be completed by the study of other kinds of chromosomal rearrangements.     

Deficiency of coagulation factors VII and X associated with deletion of a chromosome 13 (q34). Evidence from two cases with 46,XY,t(13;Y)(q11;q34)

Summary Deficiency of coagulation factors VII and X was found in two patients (Erlangen and Nancy) who shared the same chromosomal aberration 46,XY,t(13;Y)(q11;q34) with probable loss of a terminal segment of 13q. Loci involved in synthesis or constitution of these factors may be located at 13 (q34).The paper is dedicated to Prof. Dr. G. Koch on the occasion of his 70th birthday     

Trisomy 15q23----qter due to a de novo t(11;15)(q25;q23) and assignment of the critical segment

A 10 10/12-year-old boy with a de novo t(11;15)(q25;q23) leading to trisomy 15q23----qter was studied. The clinical features were compatible with other cases of distal trisomy 15q. The critical segment for this trisomy is tentatively assigned to bands 15q25----qter.     

Pure partial trisomy 5q33-->5q35 resulting from the adjacent-1 segregation of a paternal (5;14)(q33;p12) translocation.

A 14-year-old male was referred for evaluation of mental retardation with short stature and dysmorphic features. His karyotype was 46,XY,der(14)t(5;14)(q33;p12)pat, resulting in a pure partial 5q33-q35 trisomy due to the adjacent-1 segregation of a paternal balanced translocation. Paternal blood karyotype revealed a balanced translocation t(5;14)(q33;p12) retaining Ag-Nors. To date, only two cases of pure partial 5q trisomies spanning this region have been reported. Analysis of these cases and the one we report does not allow the delineation of a specific phenotype.     

Sperm chromosome analysis of two men heterozygous for reciprocal translocations: t(1;9)(q22;q31) and t(16;19)(q11.1;q13.3).

Sperm chromosome complements were analysed in two men who were heterozygous carriers of reciprocal translocations. A total of 363 sperm were karyotyped after in vitro penetration of hamster oocytes, including 180 sperm from a male with a t(1;9)(q22;q31) and 183 from a male with a t(16;19)(q11.1;q13.3). All possible 2:2 and 3:1 meiotic segregations were observed for both translocations. The frequencies of alternate, adjacent 1, adjacent 2, and 3:1 segregations were 46%, 38%, 13%, and 4% for the t(1;9) and 40%, 28%, 31%, and 1% for the t(16;19), respectively. Within the alternate segregation group, the number of normal sperm was not significantly different from the number of sperm carrying a balanced form of the translocation for either of the translocations, as expected. There was no evidence for an interchromosomal effect of either translocation, since the frequencies of numerical abnormalities unrelated to the translocation were within the normal range observed in sperm from control donors. The percentage of sperm with an unbalanced form of the translocation was 54% for the t(1;9) and 61% for the t(16;19).