A de novo translocation, 14q21q, with a microchromosome-14p21p

A familial translocation, t(14;21)(14p21p;14q21q), in a mother and her child is described. The translocation was ascertained through the birth of a Down syndrome baby with the chromosome constitution 47,XX,-14, +der 14, +der 21,t(14;21)(q11;p12) mat. A 1:3 segregation in the maternal meiosis is suggested for the evolution of the unbalanced chromosome state. The main translocated chromosome 14q21q mimics the product of a Robertsonian translocation, while the 14p21p chromosome has the morphology of a satellited microchromosome. The cytogenetic nature of this translocation is discussed.     

Molecular analysis of mosaicism for two different de novo acrocentric rearrangements demonstrates diversity in Robertsonian translocation formation

Robertsonian translocations (ROBs) involving chromosome 21 occur in about 5% of individuals with Down syndrome. ROBs are the most common chromosomal rearrangements in humans and are formed through whole arm exchanges of any two acrocentric chromosomes. The de novo formation of ROBs occurs at exceptionally high rates. The present case concerns a child with mosaic Down syndrome who has two cell lines that contain two different de novo ROBs: 45,XX,rob(14;21)(q10;q10) and 46,XX,rea(21;21)(q10;q10),+21. To elucidate the mechanisms by which the rearrangements formed, somatic cell hybrids were constructed to allow the parental origins of the chromosomes involved in the ROBs to be distinguished. The analysis of the hybrids showed that the rob(14q21q) must have formed postzygotically because it contained a maternal chromosome 14 and a paternal chromosome 21. Furthermore, hybrid analysis of the rea(21q21q) demonstrated two copies of the same chromosome from the mother and thus, by definition, was an isochromosome [i(21q)]. All free-lying chromosomes 21 isolated in hybrids were of maternal origin. These chromosomes may have originated from either of the patient's cell lines. We present four hypotheses for the formation of the two cell lines of this child. This case is part of an ongoing project to determine the mechanism(s) of de novo ROB formation and the results differ from the other de novo rob(14q21q) studied in our laboratory (n = 7) in that all previously studied translocations were maternally derived, leading to the conclusion that most de novo rob(14q21q) occur in oogenesis. The current case illustrates that other mechanisms may contribute to ROB formation. Am. J. Med. Genet. 80:252–259, 1998. © 1998 Wiley-Liss, Inc.     

Submicroscopic deletion in 14q32.3 through a de novo tandem translocation between 14q and 21p

We describe a male child with craniofacial anomalies, postnatal onset growth retardation, microcephaly, multiple minor anomalies, hearing loss, and moderate delay of mental and statomotor development. He carries a previously undescribed tandem translocation between the long arm of chromosome 14 and the short arm of chromosome 21 that arose de novo. As proven by fluorescence in situ hybridization a microdeletion not detectable with high-resolution G-banding occured in 14q32.3, the terminal band on the long arm of chromosome 14. The resulting phenotype includes most abnormalities encountered in patients with terminal 14q32.3 deletions but in addition includes some characteristics of the ring chromosome 14 syndrome. Am. J. Med. Genet. 80:443–447, 1998. © 1998 Wiley-Liss, Inc.     

Melkersson-Rosenthal syndrome and de novo autosomal t(9;21)(p11;p11) translocation

In this report we describe a 26-year-old female with the typical clinical symptoms and signs of Melkersson-Rosenthal syndrome, an autosomal dominant disorder with variable expression, and a de novo t(9;21)(p11;p11), and suggest that the "Melkersson-Rosenthal gene" is located at 9p11.     

Rubinstein-Taybi syndrome with de novo reciprocal translocation t(2;16) (p13.3; p13.3)

We describe a girl with typical Rubinstein-Taybi syndrome with apparently balanced reciprocal translocation between chromosome 2 and 16. The patient has a condition characterized by mental retardation, typical facial manifestations, broad thumbs and first toes. Cytogenetic studies of the patient showed a reciprocal translocation without visible deletion, karyotype: 46, XX, t(2;16) (p13.3; p13.3). Her parents had normal chromosomes. These results suggest that the locus of the gene for the Rubinstein-Taybi syndrome may be situated at 2p13.3 or 16p13.3.     

Segregation of chromosomes into the spermatozoa of a man heterozygous for a 14;21 Robertsonian translocation

Twenty-four spermatozoa from a man heterozygous for a Robertsonian translocation (45,XY,-14,-21,+t(14q;21q) were studied cytogenetically in order to determine the meiotic segregation of the translocation. When compared to the expected 1:1 ratio we observed a greater number of chromosomally normal sperm than sperm with the balanced translocation. Three sperm carried the translocation in an unbalanced form.     

Meiotic segregation of a 21;22 Robertsonian translocation.

In-vitro fertilization of hamster oocytes with human spermatozoa has been used to study heterozygotes for structural chromosome abnormalities. To date only four men heterozygous for Robertsonian translocations have been examined. In this study, 150 sperm chromosome complements from a 21;22 translocation were investigated. There was no evidence of an interchromosomal effect since the frequency of abnormalities unrelated to the translocation was within the range of normal donors. The frequency of unbalanced complements was 3.4%, which is similar to other Robertsonian translocations. As expected, an equivalent number of normal (n = 74) and balanced (n = 70) karyotypes was observed.     

Inherited 13/14 translocation and meta-centric microchromosome associated with trisomy 21: Report of 2 cases

Inherited chromosome abnormalities were found in two unrelated boys with Down syndrome. One patient showed trisomy 21 and a 13/14 translocation which was also present in his mother and three other family members. The other boy had a bisatellited metacentric microchromosome in addition to trisomy 21. The small marker chromosome was found in three generations in the family. In both cases, the carriers had a normal phenotype. The significance of aneuploidy and the presence of inherited karyotypic changes is discussed.     

Sotos syndrome and de novo balanced autosomal translocation (t(3;6)(p21;p21))

In this report we describe a 6-year-old boy with Sotos syndrome and a de novo apparently balanced 3/6 translocation (karyotype: 46,XY,t(3;6)(p21;p21)). Pre- and postnatal overgrowth are observed in an increasing number of conditions of variable etiology. In the Sotos syndrome autosomal dominant inheritance with variable expression has been documented. Here we discuss the importance of the cytogenetic findings and postulate a relationship between the invisible loss of chromosomal material at 3p21 and/or 6p21 and the expression of the autosomal dominant gene.     

Further characterization of 19 cases of rea(21q21q) and delineation as isochromosomes or robertsonian translocations in down syndrome

We have used 9 conventional RFLPs and 6 dinucleotide repeat polymorphisms on chromosome 21q to demonstrate that 17 of 19 cases of rea(21q21q) were consistent with isochromosomes i(21q) with the remaining 2 being true Robertsonian translocations. Eight of the 17 isochromosomes were of maternal origin and 9 cases were paternally derived. The 2 Robertsonian translocations were both maternally derived. Of the 17 isochromosomes, 7 were dicentric Wc(21q)I and 10 were monocentric M21q)l. Both rob(21q21q) were monocentric. Our findings agree with those made in 17 previously published cases of rea(21q21q). The parental origins of the i(21q) were equally divided between maternal (n = 17) and paternal (n = 15) origins. All 4 true rob(21q21q) reported to date are of maternal origin. Collectively, it appears that most homologous rearrangements of chromosome 21 are isochromosomes and only a small proportion are consistent with true Robertsonian translocations. © 1993 Wiley-Liss, Inc.     

Partial trisomy 3q due to a de novo translocation t(X;3) (p21;q12)

A patient with several congenital malformations, principally in the face, cardiovascular system and genitalia, was found to have the karyotype 46 ,X,der(X),t,X;3)(Xqter← p21::3ql2-←3qter). A comparison of the clinical and cytogenetical findings with similar cases in the literature led to the conclusion that a partial trisomy 3q is the most likely cause for the symptoms in this patient.     

Down syndrome due to 21;21 translocation in a male twin

A spontaneous 21;21 translocation resulting in features consistent with Down syndrome is reported in the first born of male fraternal twins. No history of twinning or chromosomal abnormalities in the family was noted. Any association between dizygous twinning and Down syndrome due to de novo translocation remains speculative until a sufficient pool of published data is available from study of such families.     

Segregation analysis of a translocation (16;21)(p11;q22) in a large pedigree

A large family with an inherited reciprocal translocation (16;21) is described. An unbalanced karyotype due to adjacent-1 segregation was documented in 6 cases, whereas 25 children dying within the first year of life and 4 individuals dying at later ages probably had the same abnormality. Therefore minimal and maximal risk estimates were calculated to be 6.0% and 26.5% for female, respectively, 4.8% and 33.3% for male translocation heterozygotes. Among the karyotyped phenotypically normal offspring of male as well as female carriers the ratio of normal children to balanced carriers was not different from 1:1.     

Down syndrome with biparental inheritance of der(14q21q) and maternally derived trisomy 21: Confirmation by fluorescent in situ hybridization and microsatellite polymorphism analysis

Individuals with translocation Down syndrome (DS) often inherit the rearranged chromosome from a carrier parent. DS due to inheritance of one Robertsonian or derivative (14q21q) from one parent and a second der(14q21q) in addition to a free chromosome 21 from the other parent are rarely documented in liveborn infants. Presented here is such a propositus with DS and with a unique karyotype 45,XY,der(14;21) (p11.1;p11.1)pat,der(14;21)(p11.1.;q11.1)mat, +21mat. Using conventional chromosome heteromorphisms, fluorescent in situ hybridization (FISH), and microsatellite polymorphism analyses, we established the biparental origin of the 2 der(14q21q) and the maternal origin of the extra chromosome 21 in the patient. A combination of both cytogenetic and molecular genetic techniques also enabled us to show that the 2 der(14q21q) were not identical by descent and hence the parents were nonconsanguineous. It has been a well-established fact that mothers with Robertsonian translocations have higher risk for nondisjunction than do carrier fathers. Our case, wherein the non-disjunctional event occurred in the mother, even though both parents are carriers of a 14;21 Robertsonian translocation, is yet another example of this. Am. J. Med. Genet. 70:43–47, 1997. © 1997 Wiley-Liss, Inc.     

A case of de novo i(12p) with 12q whole-arm translocation mosaicism

We report a dup(12p) due to a de novo i(12p) in a girl with mosaicism for 12q whole-arm translocations onto 7p, 7q, and 11q terminal regions. The dup(12p) syndrome was confirmed by clinical, cytogenetic, and LDH-dosage studies.     

A de novo X; 3 translocation in Rett syndrome

Rett syndrome is a neurodegenerative disorder that occurs exclusively in females. The syndrome is sporadic in most cases with the exception of a few familial cases with an inheritance pattern through maternal lines. These observations raised the possibility that Rett syndrome may be due to an X-linked dominant mutation which is lethal in the male. To evaluate this hypothesis, we have systematically performed high-resolution chromosome analysis on 28 patients with Rett syndrome searching for deletions and/or translocations. In one patient, a de novo balanced translocation was observed with the chromosome constitution of 46, X, t (X;3) (p22.11;q13.31). This finding supports the hypothesis of an X-linked dominant mutation and suggests that the Rett gene might map to distal Xp21 or proximal Xp22.     

Tetramelic mirror-image polydactyly and a de novo balanced translocation between 2p23.3 and 14q13

We report on a male infant with tetramelic mirror-image polydactyly and a de novo, balanced reciprocal translocation between 2p23.3 and 14q13. This patient suggests that a novel gene, which functions in the morphogenesis of the hands and feet along the anterior-posterior axis, may be located at 2p23.3 or 14q13. Am. J. Med Genet. 68:70–73, 1997 © 1997 Wiley-Liss, Inc.     

Site-specific reciprocal translocation,t(11;22) (q23;q11), in several unrelated families with 3:1 meiotic disjunction

We have studied 32 unrelated families with a site-specific reciprocal translocation between chromosomes 11 and 22 [t(11;22) (q23;q11)]. In translocation heterozygotes 3:1 meiotic segregation occurs and results in abnormal progeny who carry the der(22) as a supernumerary chromosome. Phenotypic findings consistent with 47,XX (or XY), +der(22), t(11;22) include mental retardation, preauricular skin tag and/or sinus, ear anomaly, palate anomaly, micrognathia, congenital heart disease, and genital anomalies in males. The frequency of abortions among offspring of male and female heterozygotes is increased. Segregation analysis shows that the risk for unbalanced offspring to be born to female heterozygotes may be as high as 10%, and that there may be a significant risk to male heterozygotes as well. The overall carrier frequency among progeny of 11;22 translocation carriers is 70.6%. The occurrence of multiple 11;22 translocation events is supported by de novo occurrence of the translocation, familial heteromorphic variants of the der(22), and varied racial and ethnic backgrounds of the families. To our knowledge, with the exclusion of centric fusion translocations, this represents the only example of nonrandom exchange in a constitutional chromosomal rearrangement.