Congenital hyperthyroidism with reciprocal translocation t(1;17)(q25;q21)

Summary The authors report a case of 1;17 translocation and request contact with colleagues who have observed similar cases.     

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.     

Partial trisomies 13 and 22 due to nondisjunction of a maternal reciprocal translocation,t(13;22)(q22;q11)

Summary A family is reported in which the propositus has an extra G-like chromosome with an unusual G-banding pattern. Cytogenetic family studies showed that the mother is a carrier of a balanced reciprocal translocation t(13;22), which does not affect the size and morphology of the chromosomes involved. The propositus has a 47,XY,+der(22),t(13;22)(q22;q11) karyotype and is therefore partially trisomic for the distal third of the long arm of chromosome 13 and for a very small part of chromosome 22. The clinical findings are presented and compared with those of other reported cases of partial trisomies 13 and 22.     

De novo balanced translocation (2;10)(q24;q22) associated with mental retardation

We report a case of a reciprocal translocation between the long arms of the 2 and 10 chromosomes observed in a 14-year-old male with mild mental impairment, compulsive and obsessive behavior. The apparently balanced translocation was characterized by fluorescence in situ hybridization and the karyotype was 46, XY, t(2;10)(q24;q22). The way by balanced chromosomal translocations can lead to a disease phenotype are reviewed and discussed.     

Cryptic translocation t(5;18) in familial mental retardation

A cryptic translocation t(5;18)(qter;qter) was detected in a large family, using a FISH-based approach combining subtelomeric probes to allow the subtelomeric regions of most chromosome ends to be analysed for deletions and balanced or unbalanced translocations. Unbalanced karyotypes (duplication 5qter/deficiency 18qter) resulted in a previously undescribed association of moderate to severe mental retardation, microcephaly, pre- and postnatal growth retardation, distinct facial dysmorphism, narrow auditory canals, genital hypoplasia, left heart hypoplasia in one patient and severe behaviour difficulties in another. Some of the features observed in affected individuals are characteristic of known syndromes involving either 18q (growth deficiency, nystagmus, narrow auditory canals, genital hypoplasia, behaviour problems in 18q deletion syndrome) or 5q (umbilical and inguinal hernias, congenital heart defects in distal 5q trisomy).     

Sotos syndrome with a balanced reciprocal translocation t(2;12)(q33.3;q15)

A balanced reciprocal translocation, 46,XY, t(2;12), was detected in a male infant who had the characteristic features of Sotos syndrome. His father's karyotype was normal, but his mother and an older brother had the same chromosomal abnormality without a history or clinical features of Sotos syndrome.     

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.     

Partial trisomy 2q and familial translocation t(2;12)(q31;q24)

Summary Report is given of a boy with trisomy of the distal part of the long arm of chromosome 2 (q31ter) due to a balanced 2/12 translocation in the mother: 46,XX,t(2;12) (q31;q24). Other phenotypically normal carriers of this balanced translocation are the patients sister and grandfather. The patient shows a variety of dysplastic signs mainly of the face.     

Meiotic and sperm chromosome studies in a reciprocal translocation t(1;2)(q32;q36)

Summary Meiotic and sperm chromosomes were studied in a man heterozygous for a reciprocal translocation t(1;2)(q32; q36). Forty-five meiotic metaphase I cells were obtained from semen samples: 86.6% were 22,XY,IV and 13.3% had synaptic anomalies that affected all or some of the bivalents. The quadrivalents observed had a ring configuration (92.3%) or a chain configuration (7.7%). A total of 105 sperm chromosome complements were analyzed: 41% resulted from an alternate segregation, and the percentage of unbalanced sperm was 59%; most of them (71%) resulted from an adjacent 1 segregation. The frequency of anomalies unrelated to the translocation (5.7% numerical and 14.1% structural anomalies) were within the normal range for control donors. There was a good correspondence between the percentage of cells with a ring IV (92.3%) and the proportion of 2:2 segregations (88.6%) and between the percentage of chain IV (7.7%) and the incidence of 3:1 segregations (11.4%).     

Antenatal diagnosis of a de novo reciprocal translocation 46,XX,t(3;7)(q21;q11)

Summary A pedigree is described that includes three cases of periodic hypokalemic paralysis. Apparently, the disease has arisen by de novo mutation in a father of two affected daughters, who, however, is not affected himself. This is unexpected, since in males the disorder is generally inherited as a fully dominant trait. Therefore we propose that these findings result from an early somatic or a half-chromatid mutation.     

Fine mapping of the constitutional translocation t(11;22)(q23;q11)

Translocation t(11;22)(q23;q11) is the most common constitutional reciprocal translocation in man. Balanced carriers are phenotypically normal, except for decreased fertility, an increased spontaneous abortion rate and a possible predisposition to breast cancer in some families. Here, we report the high resolution mapping of the t(11;22)(q23;q11) breakpoint. We have localised the breakpoint, by using fluorescence in situ hybidisation (FISH) walking, to a region between D11S1340 and WI-8564 on chromosome 11, and D22S134 and D22S264 on chromosome 22. We report the isolation of a bacterial artificial chromosome (BAC) clone spanning the breakpoint in 11q23. We have narrowed down the breakpoint to an 80-kb sequenced region on chromosome 11 and FISH analysis has revealed a variation of the breakpoint position between patients. In 22q11, we have sequenced two BACs (BAC2280L11 and BAC41C4) apparently mapping to the region; these contain low copy repeats (LCRs). Southern blot analysis with probes from BAC2280L11 has revealed different patterns between normal controls and translocation carriers, indicating that sequences similar/identical to these probes flank the translocation breakpoint. The occurrence of LCRs has previously been associated with genomic instability and "unclonable" regions. Hence, the presence of such repeats renders standard translocation breakpoint cloning techniques ineffective. Thus, we have used high resolution fiber-FISH to study this region in normal and translocation cases by using probes from 22q11, LCRs and 11q23. We demonstrate that the LCR containing the gap in 22q11 is probably substantially larger than the previous estimates of 100 kb. Using fiber-FISH, we have localised the breakpoint in 22q11 to approximately 20-40 kb from the centromeric border of the LCR (i.e. the telomeric end of AC006547) and have confirmed the breakpoint position on 11q23.     

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.     

Partial trisomy 2q and familial translocation t(2;18)(q31;p11)

Summary This report describes a malformed infant with distal 2q trisomy/ distal 18p monosomy due to adjacent segregation of a familial t(2;18). The rearrangement was present in four generations, and linkage studies were performed.     

An azoospermic male with reciprocal translocation t(1;15)(q11;p11)

Summary The authors report on a case of 1;15 translocation and request contact with any colleagues who have observed similar cases.