Blepharophimosis sequence and de novo balanced autosomal translocation [46, XY,t(3;4)(q23;p15.2)]: Possible assignment of the trait to 3q23

We report on a boy with the blepharophimosis sequence and de novo, apparently balanced reciprocal translocation between 3q23 and 4p15.2 [46, XY,t(3;4)(q23;p15.2)de novo]. Possible assignment of this autosomal dominant disorder is discussed. A 3q23 band is a more preferable gene locus of the blepharophi mosis sequence, based on the comparison of clinical manifestations between 4p- and 3q-syndromes.     

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.     

Myotonic dystrophy and autosomal balanced translocation t(2; 20) (p21; q11)

The present paper reports the concurrence of Myotonic Dystrophy and an autosomal balanced translocation t(2;20)(p21;qll), both occurring de novo in a 21–year-old female.     

Blepharophimosis,ptosis, epicanthus inversus syndrome,a new case associated with de novo balanced autosomal translocation [46,XY,t(3;7)(q23;q32)]

This paper reports a further case of blepharophimosis, ptosis, epicanthus inversus (BPES) syndrome associated with a reciprocal translocation [46,XY,t(3;7)(q23;q32)], involving band 3q23. This case supports the assignment of a BPES gene(s) to the 3q23 region. © 1994 Wiley-Liss, Inc.     

Craniosynostosis and hemizygosity for D7S135 caused by a de novo and apparently balanced t(6;7) translocation

Craniosynostosis (CRS) is frequently seen in the del(7p) syndrome, and the gene for this cranial anomaly (CRS1) has been assigned to 7p21. We present a 3-year-old boy with CRS involving the sagittal and coronal sutures, who had a de novo and apparently balanced translocation, t(6;7)(q16.2;p15.3). Southern blot analysis of several loci on 7p14 → pter showed that the patient was heterozygous for HOX1I and IL6, possibly homozygous for D7S149, but hemizygous for D7S135 with a loss of the paternal allele. These findings suggest the localization of a candidate gene for CRS1 to be on 7p15.3 in the close proximity to the D7S135 locus. © 1994 Wiley-Liss, Inc.     

Congenital scoliosis (hemivertebra) associated with de novo balanced reciprocal translocation, 46,XX,t(13;17)(q34;p11.2)

We report on an 8-year-old girl with congenital scoliosis (segmented hemivertebra between the second and third lumbar vertebrae) and psychomotor developmental delay. She has a de novo reciprocal translocation, t(13;17)(q34;p11.2). Congenital scoliosis is one type of structural spine deformation and hemivertebra is the most common anomaly causing congenital scoliosis. The cause and the mode of inheritance of hemivertebrae are unknown. Our patient has a de novo balanced chromosome aberration and retains two copies of the LLGL gene, which is usually lacking in patients with Smith-Magenis syndrome (SMS). Since some SMS patients who showed a deletion at 17p11.2 had congenital scoliosis, it is likely that one (17p11.2) of the breakpoints in our patient is a candidate region for a hemivertebra locus. Am. J. Med. Genet. 73:244–246, 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.     

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.     

Partial trisomy 6p from a de novo translocation (6; 18) with variable mosaicism in different tissues

Partial trisomy 6p is regarded as a distinct phenotype with short stature, failure to thrive, facial dysmorphisms with blepharophimosis, mental retardation and other malformations. An 18-month-old girl with typical features of partial trisomy 6p showed a de novo unbalanced translocation resulting in partial trisomy 6p21 to pter and partial monosomy 18p11 to pter. The translocation was observed in all fibroblasts analyzed, but only in 6% of the peripheral lymphocytes.     

A new case of "complete" trisomy 5p with isochromosome 5p associated with a de novo translocation t(5;8)(q11;p23)

A boy with a de novo translocation t(5;8)(q11;p23) and an isochromosome 5p is described. The main clinical features found in the complete trisomies 5p are reviewed and the mechanisms of the chromosomal rearrangements involving centromeric and telomeric regions are discussed.     

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.     

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.     

Sotos syndrome associated with a de novo balanced reciprocal translocation t(5;8)(q35;q24.1).

We describe a de novo balanced reciprocal translocation between the long arms of chromosomes 5 and 8 [46,XX,t(5;8)(q35;q24.1)] in a 15-month-old girl with a typical Sotos syndrome phenotype. Involvement of the 5q35 region was previously reported (Maroun et al. [1994: Am J Med Genet 50:291-293]) as one of translocation breakpoints in the present patient. We suggest that the gene responsible for Sotos syndrome is located to a distal long-arm region of chromosome 5.     

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.     

Rubinstein‐Taybi syndrome caused by a de novo reciprocal translocation t(2;16)(q36.3;p13.3)

Rubinstein‐Taybi syndrome (RTS) is a multiple congenital anomalies and mental retardation syndrome characterized by facial abnormalities, broad thumbs, and broad big toes. We have shown previously that disruption of the human CREB‐binding protein (CBP) gene, either by gross chromosomal rearrangements or by point mutations, leads to RTS. Translocations and inversions involving chromosome band 16p13.3 form the minority of CBP mutations, whereas microdeletions occur more frequently (∼10%). Breakpoints of six translocations and inversions in RTS patients described thus far were found clustered in a 13‐kb intronic region at the 5′ end of the CBP gene and could theoretically only result in proteins containing the extreme N‐terminal region of CBP. In contrast, in one patient with a translocation t(2;16)(q36.3;p13.3) we show by using fiber FISH and Southern blot analysis that the chromosome 16 breakpoint lies about 100 kb downstream of this breakpoint cluster. In this patient, Western blot analysis of extracts prepared from lymphoblasts showed both a normal and an abnormal shorter protein lacking the C‐terminal domain, indicating expression of both the normal and the mutant allele. The results suggest that the loss of C‐terminal domains of CBP is sufficient to cause RTS. Furthermore, these data indicate the potential utility of Western blot analysis as an inexpensive and fast approach for screening RTS mutations. Am. J. Med. Genet. 92:47–52, 2000. © 2000 Wiley‐Liss, Inc.     

Familial t(6;21)(p21.1;p13) translocation associated with male-only sterility

A 38-year-old male with primary infertility was referred for cytogenetic investigation. Karyotype analysis revealed a 46,XY,t(6;21)(p21.1;pl3) translocation. The Ag-nucleolar organizer regions (NORs) banding technique demonstrated that the 21p NORs were retained in the derivative and actively transcribed. Family studies showed that three brothers, two sisters and their mother carried the t(6;21). All carrier males suffered from primary infertility with severe oligoasthenoteratospermia or azoospermia, whereas at least two of the three carrier women were fertile. The region of the translocation breakpoint was narrowed down cytogenetically and by fluorescence in situ hybridisation as 21p13 and 6p21.1. Southern blot analysis showed that the gene ZNF165, which maps to this region and which is specifically expressed in the testis, was not disrupted by the translocation. However, studies performed on testicular biopsy showed spermatocyte meiosis anomalies. We discuss the possible mechanisms by which the translocation might affect meiosis in spermatogenesis and lead to infertility.     

De novo balanced translocation (6;18)(q21;q21.3) in a patient with heterotaxia

We report on a sporadic case of heterotaxia with a de novo chromosome structural abnormality. The patient had inversely located heart (dextrocardia), stomach, duodenum, and cecum. In addition, she had cerebral atrophy, hypertelorism with telecanthus, infraorbital skin furrows, ear-lobe grooves, prominent maxilla and teeth, large carp mouth, short fifth fingers with limited flexion, generalized hypotonicity, and severe psychomotor retardation. High-resolution chromosome banding analysis demonstrated an apparently balanced translocation: 46,XX,t(6;18)(q21;q21.3). It is hypothesized that both heterotaxia and the chromosomal abnormality in the patient are causally related and a putative situs determining gene has been disrupted by the chromosome break, i.e., a position effect or a cryptic deletion at around the breakpoints. The translocation in our patient may be a good source for positional cloning of the gene. © 1996 Wiley-Liss, Inc.     

Partial trisomy 6p due to maternal t(1;6) translocation

Partial trisomy 6p with duplications ranging from 6p21 to 6p25 is emerging as an established syndrome. A case of duplication of segment p22-p25 of the short arm of chromosome 6 as the result of a maternal t (1;6)(q44;p22.2) translocation in a mentally retarded girl with congenital anomalies is reported here. The associated phenotypic anomalies are compared with other reported cases of duplication 6p involving adjacent regions.