The 11q;22q translocation: A European collaborative analysis of 43 cases

Summary Translocation between the long arms of chromosomes 11 and 22 is usually detected in offspring with an unbalanced karyotype following a 3:1 disjunction resulting in partial trisomy. Since by the end of 1976 it was suspected that this translocation might be more frequent than one would deduce from published reports, it was decided to call for a collaborative effort in Europe to collect unpublished cases. In response, 42 cases were collected in Europe, and one case from New Zealand was added. The following countries were represented with the number of cases indicated in parentheses: Czechoslovakia (2), Denmark (4), Finland (3), France (6), Germany (1), Italy (5), The Netherlands (9), Sweden (6), United Kingdom (4), Yugoslavia (2). The wide geographical distribution indicates a multifocal origin of the translocation. Among the unpublished cases, 31 were ascertained as unbalanced carriers [47,XX or XY,+der(22),t(11;22)] and 12 as balanced balanced carriers [46,XX and XY,t(11;22)]. Among the published cases, 10 were ascertained in unbalanced and 3 in balanced carriers. The breakpoints of the translocations indicated by the contributors varied, the most frequently reported being 11q23;22q11 (25 cases), followed by q25;q13 (10 cases). While the first one seems more likely, it was not possible to decide whether the breakpoints were the same in all cases.All 32 probands with unbalanced karyotypes had inherited the translocation, 31 from the mother and only 1 from the father. This ratio became 43:1 when the published cases were added. A segregation analysis revealed that in families ascertained through probands with unbalanced karyotypes there was a ratio of carriers to normal (all karyotyped) 54:55, not a significant difference. The formal maximum (minimum) recurrence risk for this unbalanced translocation was calculated to be 5.6% (2.7%). When the ascertainment was through a balanced proband, the maximum risk was 2.7%. The risk was calculated as 5.7% for female and 4.3% for male carriers. The mean family size was 1.67 for the offspring of female carriers and 0.78 for the offspring of male carriers. This significant difference suggests that heterozygosity for the translocation reduces fertility in males. Indeed, several of the probands with balanced karyotypes were ascertained because of sub- or infertility. Only 2 de novo translocations were found among the 59 probands, and both, were among the 12 cases ascertained as balanced carriers. The source, quality, and quantity of the clinical data for the subjects with unbalanced karyotypes were variable, and no definite conclusions were possible about phenotypes. The following signs were recorded in 10 or more of the 45 cases: low birth weight, delayed psychomotor development, hypotonia, microcephaly, craniofacial asymmetry, malformed ears with pits and tags, cleft palate, micro-/retrognathia, large beaked nose, strabismus, congenital heart disease, cryptorchidism, and congenital dislocation of the hip joints. Many signs were similar to those considered typical of trisomy 11q, and the phenotype coincided almost completely with the presumptive phenotype of complete trisomy 22. No cases with coloboma was recorded, while other signs of the cat-eye syndrome were found in several probands. This might indicate that individuals with the cat-eye syndrome and carriers of the unbalanced 11/22 translocation have the same segment of 22 in triplicate plus or minus another chromosome segment.     

A jumping translocation (5p;15q), (8q;15q), and (12q;15q) (author's transl)]

Three balanced karyotypes (5p;15q), (8q;15q), and (12q;15q) were found simultaneously in a child with the Willi-Prader syndrome. The hypothesis is presented of a "jumping# translocation by affinity of telomeric and interstitial palindromes. The relationship between the Willi-Prader syndrome and a juxtacentric anomaly of the long arm of chromosome 15 is discussed.     

Partial trisomy of 11 and 22 due to familial translocation t(11;22) (q23;q11), inherited in three generations

Summary A 1-year-old girl with partial trisomy of 11 (q23qter) and 22 (pterq11) is presented. She had severe mental retardation, cleft palate, congenital heart disease, congenital dislocation of the hip, and other anomalies.The extra acrocentric chromosome was identified as der(22),t(11;22) (q23;q11) from a familial translocation and by G-and R-banding methods. The mother and the maternal grandfather were carriers of balanced rcp(11;22) (q23;q11) translocations.The possible relations between phenotypic features and the karyotypes of partial trisomy 11 and 22 are discussed.     

Tertiary trisomy (22q11q),47,+der(22),t(11;22)

Summary We describe a case of tertiary trisomy (22q11q) 47,XX,+der(22),(22pter22q13: : 11q2511qter) in a child with mental retardation, cleft palate, and congenital heart disease resulting from 3: 1 meiotic nondisjunction in a maternal (11;22) translocation carrier. The clinical findings in previously reported cases are reviewed and compared with the features of reported patients with partial trisomy 11q and trisomy 22 syndromes. Half of the ten reported families had additional balanced translocation carriers who may have an increased risk of having a liveborn child with an MCA/MR syndrome, although none have been reported to date.     

Two familial cases with trisomy 15q dist due to a rcp(5;15)(p14;q21)

Summary A trisomy of the distal long arm of chromosome 15 (q21qter) resulting in similar phenotypic and developmental abnormalities in two related children (a boy and a girl) is described. The chromosome defect was due to malsegregation of a balanced translocation (5;15)(p14;q21) in one of the parents. It was inherited in four generations and accompanied by recurrent miscarriages. Comparison of these patients with four previously published cases of trisomy 15q dist reveals a pattern of common features including: microdolichocephaly with characteristic strikingly protuberant occiput and predominance of the visceral over the cerebral cranium; peculiar facial dysmorphism—narrow antimongoloid palpebral fissures; large, malformed, low-set ears; micrognathy; long philtrum; short neck; cardiopathy; profound encephalopathy with lack of suck and swallow reflexes; and no growth retardation.     

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).     

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.     

Partial trisomy 14q due to familial t(14q-, 11q+) translocation

Summary A malformed male newborn with partial trisomy for the distal part of the long arm chromosome 14 (14q₂₃14qter) is described. This anomaly arose as a segregation product of a balanced t(14q-, 11q+), translocation in the father.     

2:12 (p25;q21) translocation classed at first as 2/X]

A balanced translocation t(2;12)(p25;q21) was observed in a girl with mental retardation and several somatic abnormalities. The problems of phenotype-karyotype correlations are discussed.     

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.     

A balanced translocation t(11;16)(q13;p11), a cytogenetic study and an attempt at gene localization

Summary Members of three generations of a single family were examined and found to have a balanced translocation t(11;16)(q13;p11). Cytogenetic investigation and investigation of a number of gene markers is consistent with the current view that the Hp- locus is situated in the proximity of band 16q22.     

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.     

Balanced de novo translocation t(6;7)(p25;q31) and cleft palate as an isolated finding

We report a prenatally diagnosed balanced de novo translocation t(6;7)(p25;q31). Physical examination of the baby born at term revealed only a posterior cleft palate. Laboratory examinations and radiologic investigations were found normal. Two years follow-up of the patient showed her mental and motor development was appropriate with her age. Our report is the first observation on balanced de novo translocation t(6;7)(p25;q31) and cleft palate. Association of this translocation and cleft palate has not been reported previously.     

Adjacent 2 meiotic disjunction. Report of a case resulting from a familial 13q;15q balanced reciprocal translocation and review of the literature

Summary An abnormal short-lived female infant with almost complete trisomy 13 (pterq32 or 33) and partial monosomy 15 (pterq14 or 15) resulting from an adjacent 2 meiotic disjunction of a paternal reciprocal translocation is described. Cases with monosomy of chromosome 15 material are reviewed. It appears likely that monosomy of an interstitial long arm segment, approximating to 15q2124, imparts the lethality associated with the full monosomic condition. Adjacent 2 disjunction in man has been further characterised by reviewing the literature.     

Cytogenetic mapping of five YAC clones to human chromosome region 2q31 --> q32.1 in relation to the FRA2G common fragile site

In this work, five YAC clones have been mapped by fluorescent in situ hybridization (FISH) to human chromosome region 2q31 q32.1 and ordered in relation to each other and to the FRA2G common fragile site. YAC clones that span the fragile site have been identified. Moreover a deleted HOXD 13 gene has been identified on the 942D2 YAC.     

Partial trisomy of distal 5q and partial monosomy of Xp as a result of mating between two translocation carriers: a female with a balanced translocation t(X;5)(p11;q31) and a male with a der(13;14)(q10;q10)--a case report and a family study

This paper presents the family of a dysmorphic child with the phenotypic features of Turner's syndrome and 5q trisomy, whose parents are both carriers of a balanced translocation. The parents' karyotypes are 46,X,t(X;5)(p11.1;q31) and 45,XY,der(13;14)(q10;q10), respectively.     

Identification of a familial robertsonian translocation t(13q14q) by means of thermic moderated denaturation

Summary A familial DD translocation was identified as a translocation t(13q14q) by means of a thermic moderated denaturation banding technique.     

Partial trisomy 17q

Summary A 15-year-old deeply mentally retarded male is described with partial distal 17q trisomy (17q2217qter), as the result of a de novo 17q/21p translocation. Differential Ag-staining showed that the satellites of chromosome 21 were included in the translocation chromosome.     

Molecular detection of a translocation (Y;11)(q11.2;q24) in a 45,X male with signs of Jacobsen syndrome

Summary A 45,X karyotype was found in a boy with dysmorphic features, hypoglycaemia and pancytopenia. DNA analysis showed the presence of the Y-chromosomal DNA sequences SRY, ZFY, DYZ4, DYZ3 and DYS1. Using fluorescent in situ hybridization, we located DYZ4 and DYZ3 on chromosome llqter and concluded that a de novo translocation (Y;11)(q11.2;q24) with a deletion of 11q24qter and a deletion of Yq11.2Yqter were present; Jacobsen syndrome and azoospermia are associated with these deletions. Signs of Jacobsen syndrome were observed in the patient.