Distal trisomy 14 (q24 --> qter) and aorto-pulmonary window: a case report and review of the literature

A newborn female with partial trisomy for the distal part of the long arm of the chromosome 14 (14q24 --> qter) resulting from a paternal balanced translocation (3;14) is described. We compare her phenotype with eight other individuals with trisomy 14q24 --> qter.     

Distal trisomy 10q/partial monosomy 14q: an unusual clinical picture

A case of twin boy with partial trisomy for the distal part of the long arm of chromosome 10 (10q24-->qter) and a concomitant monosomy 14(q32-->qter) is reported. The chromosomal abnormalities resulted from a paternal balanced translocation involving chromosomes 10 and 14. An additional clinical feature was observed, viz. hypoplastic lungs. The proband's phenotype was compared to previously reported patients with partial trisomy 10q or 14q deletion.     

Double partial trisomy of 6p23-pter and 9pter-q21.2 in a neonate resulting from 4:2 meiotic segregation of a maternal complex t(6;7;9)(p23;p15;q21.2) translocation

We report, a newborn presenting multiple congenital abnormalities with karyotype; 47,XY,der(7)t(6;7)(pter-p23::p15-->qter),+der(9)t(7;9)(pter-->p15::q21.2--> pter)t(6;7;9)(p23;p15;q21.2)mat[20]. The mother and her phenotypically normal daughter were carriers of a complex chromosomal rearrangement with karyotypes; 46,XX,t(6;7;9)(p23;p15;q21.2)[20]. Paternal chromosomes were normal. In our case the extra derivative chromosome was the result of a 4:2 segregation of the chromosomes involved in translocation during oogenesis. Double partial trisomy in newborns resulting from 4:2 segregation is a rare event, and double partial trisomies of the 6p23-pter and trisomy 9pter-q22 regions have not reported to date.     

Molecular cytogenetic identification and characterization of a de novo supernumerary neocentromeric derivative chromosome 13

We report a young girl with microphthalmia, conductive deafness, aortic isthmus stenosis, laryngomalacia, and laryngeal stenosis carrying a de novo supernumerary neocentromeric derivative chromosome 13. For the precise identification and characterization of the eu- and heterochromatic content of the marker chromosome, straightforward molecular cytogenetic analyses were performed, such as chromosome microdissection, FISH with different probes (e.g. wcp, alphoid centromeric probes, BAC), centromere-specific multicolor FISH (cenM-FISH), and multicolor banding (MCB). The analyses demonstrated that the marker consisted of an inverted duplication (partial tetrasomy) of the distal portion of chromosome 13 that was separated from the endogenous chromosome 13 centromere. Using an all-centromere probe and multicolor cenM-FISH, no alpha-satellite DNA hybridization signal was detectable on any portion of the derivative chromosome. The presence of a functional and active neocentromere on the derivative chromosome 13 was confirmed by positive immunofluorescence signals with CENP-C antibodies. BAC-FISH confirmed the cytogenetic localization of the neocentromere in band 13q31.3. Thus the patient had a mosaic conventional karyotype mos 47,XX,+inv dup(13)(qter-->q21.3::q21.3-->q31.3-->neo-->q31.3-->qter)[6]/46,XX [49].     

Spectral karyotyping and fluorescence in situ hybridization analysis of de novo partial trisomy 7p (7p21.2-->pter) and partial monosomy 12q (12q24.33-->qter)

An 8-year-old boy presenting with hypotonia, moderate mental retardation, developmental delay, and psychomotor retardation is reported. Magnetic resonance imaging of the brain at age 3 years revealed a Dandy-Walker variant. Cytogenetic analysis of the peripheral blood revealed a derivative chromosome 12 with unknown additional material attached to the distal region of the long arm of chromosome 12. The parental karyotypes were normal. Spectral karyotyping (SKY) using the 24-color SKY probes and fluorescence in situ hybridization (FISH) using the specific 7p, 7q, 12p, and 12q telomeric probes confirmed a duplication of distal 7p and a deletion of terminal 12q. The karyotype of the proband was designated as 46,XY.ish der(12)t(7;12) (p21.2;q24. 33)(SKY+, 7pTEL+, 12qTEL-). The present case provides evidence for the association of partial trisomy 7p (7p21.2-->pter) and partial monosomy 12q (12q24.33-->qter) with a cerebellar malformation and the usefulness of SKY and FISH in the identification of a de novo aberrant chromosome resulting from an unbalanced translocation.     

Two sibs with duplication of 4q31-->qter due to 3:1 meiotic disjunction and mild phenotype

Two sibs with duplication of 4q31-->qter due to 3:1 meiotic disjunction and mild phenotype: Clinical and cytogenetic findings in two sibs with partial duplication of 4q31.3-->qter and 21q11.2-->pter are reported. These patients are rare cases of reoccurrence of those partial trisomies due to 3:1 segregation of a maternal balanced translocation. A review of the literature reporting cases of trisomy of the 4q31-->qter segment is also made; previously reported cases mostly in addition have deletions of other chromosomes resulting from adjacent segregation of balanced translocation. The findings of our study confirm the high risk for offspring with unbalanced rearrangements in women with reciprocal translocation involving acrocentric and short chromosome segments. The study also points out that duplication of 4q31-->qter may go along with only mild phenotypic findings if there is no significant additional aneuploidy of the other chromosome involved in the rearrangement.     

Partial trisomy 8p (8p11.2-->pTER) and deletion of 13q (13q32-->qTER): case report

We report a female infant with partial trisomy 8p (8p11.2-->pter) and deletion of 13q (13q32-->qter). She was born with mild hypotonia, intrauterine growth retardation, microcephaly, micrognathia, large low set ears, pectus excavatum, anteriorly placed anus, and bilateral clinodactyly. Echocardiography showed left ventricular hypertrophy, bicuspid aortic valve, dilatation of the aorta and pulmonary artery, and prolapse of atrio-venticular valve leaflets. Cytogenetic investigation of her sister and her father showed that the altered region resulted from a balanced translocation between the part of the long arm of chromosome 13 and short arm of chromosome 8. In partial trisomy 8p, the clinical picture of the patients comprises hypotonia, structural brain abnormalities, facial anomalies including a large mouth with a thin upper lip, a high arched palate, a broad nasal bridge, an abnormal maxilla or mandible, malformed, low set ears, and orthopedic anomalies. Although patients with proximal deletions of 13q that do not extend into band q32 have mild to moderate mental and growth delays with variable minor anomalies, patients with more distal deletions including at least part of band q32 usually have major malformations such as retinoblastoma, mental-motor growth retardation, malformation of brain and heart, anal atresia, and anomalies of the face and limbs. To our knowledge partial trisomy 8p and partial monosomy of 13q have not been reported previously in the same person.     

Partial trisomy 11q syndrome (11q23.1-->11qter) due to de novo t (11q; 13q) detected by multicolor fluorescence in situ hybridisation

In this report we describe the identification of a de novo 46, XX, 13q + by multicolour fluorescence in situ hybridisation (M-FISH), as a partial distal 11q trisomy (11q23.1-->11qter). The clinical phenotype association with this distal 11q trisomy is briefly reviewed.     

Distal trisomy of 10q. Report of a new case of duplication 10q25.2-25.3-->qter defined by FISH

In the present work, we report on a 2.5-year-old male patient with typical clinical features of partial trisomy of the distal third of chromosome 10 long arm. The karyotype was: 46,XY, dir dup(10)(q25.2-25.3-->qter). The identification of the duplicated segment was carried out by the fluorescence in situ hybridization technique using region-specific probes. The proband's phenotype is compared with previously reported cases.     

Partial trisomy of the distal part of 10q: a report of two Egyptian cases

Partial trisomy of the distal third of the long arm of chromosome 10 is a well defined but rare syndrome. Most cases result from an unbalanced translocation. Growth retardation, developmental delay and characteristic dysmorphic features are well described in the syndrome. This report includes 2 Egyptian cases with partial 10q trisomy involving different breakpoints. Cases were subjected to full clinical examination and detailed cytogenetic analysis using conventional and FISH studies. Results showed that the karyotype of case 1 was 46,XX,der(7)t(7;10)(p22;q23).ish(wcp7+;wcpl0+) and the karyotype of case 2 was 46,XX,der(7)t(7;10)(p22;q25).ish(wcp7+;wcp 10+). The chromosomal abnormalities in case 1 resulted from a paternal balanced translocation while case 2 resulted from a maternal balanced translocation involving chromosomes 10 and 7 in both cases. The probands' phenotypes were correlated to the breakpoints and compared to previously reported cases with partial trisomy 10q. Both cases had the well characterized phenotype of the distal trisomy of 10q in the form of mental retardation, microcephaly, characteristic dysmorphic facies and limb anomalies as trisomy in both cases involved the 10q25-->qter region. However, case 1 with 10q23-->qter duplication showed more severe clinical manifestations than case 2 with less extensive 10q25-->qter trisomy. These included severe failure to thrive, cardiac involvement and death from respiratory and heart failure. This study confirmed that unbalanced chromosome regions of the long arm of chromosome 10 play an important role in developmental malformations and that a more severe form is associated with involvement of 10q23. It also emphasizes the importance of increasing public awareness regarding these chromosomal rearrangements and the importance of genetic counseling and prenatal diagnosis to avoid recurrences and associated family stress. This was clearly demonstrated in the second family in this study as the couple refused any follow up or further investigations due to religious beliefs despite their social and educational level.     

A de novo (1;2;3;15;18) chromosome rearrangement with six nonreciprocal translocations

A de novo complex chromosome rearrangement (CCR) found in a phenotypically abnormal boy was characterized by G-bands, FISH with subtelomere probes, and M-FISH. The G-banding analysis revealed involvement of chromosomes 1, 2, 3, 15, and 18 with (at least) eight breakpoints, five nonreciprocal translocations (1q --> 2q --> 8q --> 15q --> 2p --> 1q), and a 3p insertion into the der(2); there was also a presumptive deletion of 1q41. The 5 derivatives were described as follows: der(1)(1pter --> 1q32.3?::2p21--> 2pter),der(2)(1qter --> 1q42?::2q24.2 --> 2p21::3p13 --> 3p26::15q15 --> 15qter),der(3)(3qter --> 3p13:),der(15)(15pter --> 15q15::18q11 --> 18qter),der(18)(18pter --> 18q11::2q24.2 --> 2qter). The molecular assays confirmed the segmental composition of each derivative and documented the localization of most relevant telomeres. In addition to the novelty of the 1, 2, 3, 15 and 18 combination, this CCR may also be unique in the sense that it represents a cluster of 6 nonreciprocal transpositions regardless of the occurrence (or lack thereof) of secondary unbalances. Finally, there appears to be an excess of CCRs in fetuses conceived by intracytoplasmic sperm injection.     

A new case of partial 14q31.3-qter trisomy due to maternal pericentric inversion

Chromosome 14 is often involved in chromosome rearrangements, although pericentric inversions are rare. Here we report a mother carrying a pericentric inversion of chromosome 14, and her daughter with recombinant chromosome characterized by a partial distal 14q trisomy. Principal clinical findings of the child include facial anomalies, microcephaly, developmental delay, hypotonia and cardiac malformation. Her final karyotype was 46,XX,rec(14)dup(14q)inv(14)(p12q31)mat[20], arr 14q31.3qter(85,427,839–106,356,482)x3. This report brings new data about clinical features of partial 14q trisomy and molecular analysis enables the visualization of genes involved in the segment duplicated.     

An unusually large 5q duplication in an adult female subject: spreading of inactivation and in vitro instability of the derivative Xp/5q chromosome

An unbalanced translocation resulting in an unusually large partial 5q trisomy (5q11-5qter) and partial Xp monosomy (Xp11-Xpter) is reported in a 24 yr old woman with phenotypic abnormalities including gonadal dysgenesis and mental retardation. The karyotypes of the parents and the brother were found normal. Peripheral blood stimulated lymphocytes and cutaneous fibroblasts of the proband exhibited constantly, after BrdU incorporation, selective inactivation of the derivative X;5 chromosome spreading to the 5q duplicate segment. A variety of numerical and structural changes involving the derivative chromosome were observed in about 10% of cells of the cultured lymphoblastoid line established from the subject's lymphocytes. The extended 5q duplication, according to the literature, is generally accompanied by a severe phenotype and by developmental failure; it is therefore believe that genetic inactivation of the 5q duplicated region permitted the proband's development to adult age, despite the profound chromosomal imbalance.     

A complex chromosomal rearrangement with a translocation 4;10;14 in a fertile male carrier: ascertainment through an offspring with partial trisomy 14q13-->q24.1 and partial monosomy 4q27-->q28 [corrected

Complex chromosomal rearrangements (CCRs) are usually associated with infertility or subfertility in male carriers. If fertility is maintained, there is a high risk of abnormal pregnancy outcome. Few male carriers have been identified by children presenting with mental retardation/congenital malformations (MR/CM) or by spontaneous abortions of the spouses. We report a de novo CCR with five breakpoints involving chromosomes 4, 10 and 14 in a male carrier who was ascertained through a son presenting with MR/CM due to an unbalanced karyotype with partial trisomy 14 and partial monosomy 4. The child has a healthy elder brother. In the family history no abortions were reported. No fertility treatment was necessary. Cytogenetic analysis from the affected son showed a reciprocal translocation t(4;10) with additional chromosomal material inserted between the translocation junctions in the derivative chromosome 10. The father showed the same derivative chromosome 10 but had additionally one aberrant chromosome 14. Further molecular cytogenetic analyses determined the inserted material in the aberrant chromosome 10 as derived from chromosome 14 and revealed a small translocation with material of chromosome 4 inserted into the derivative chromosome 14. Thus the phenotype of the son is supposed to be associated with a partial duplication 14q13-->q24.1 and a partial monosomy 4q27-->q28. Including our case we are aware of eleven CCR cases with fertile male carriers. In eight of these families normal offspring have been reported. We propose that exceptional CCRs in fertile male carriers might form comparatively simple pachytene configurations increasing the chance of healthy offspring.     

A severely mental and motor retarded boy with monosomy 9pter-->p22 trisomy 10q26-->qter due to paternal reciprocal translocation 46,XY,t(9;10)(p23;q26)

We report on a twenty-two months old male patient with hypotonia, mental and motor retardation and trigonocephaly. Standard GTG banding chromosomal analysis (from metaphyses of a periferal blood lymphocyte culture) showed 46,XY, der(9) monosomy 9pter-->p22, trisomy 10q26--> qter karyotype. This unbalanced translocation resulted from the father's t(9,10) (p22;p26) karyotype. Deletions of the terminal part of 9p and partial trisomy of chromosome 10q are rare chromosomal disorders. To our knowledge, this is the first case report in the literature of a deletion of 9pter-->p22.3 and a duplication of 10q26-->qter. We assume that the clinical anomalies are due to der(9) monosomy 9pter-->p22, trisomy 10q-->26qter.     

Molecular cytogenetic characterization of a familial balanced reciprocal translocation t(11;18) (q13.3; q23) associated with pregnancy wastage

A new male patient associated with a pregnancy wastage was detected in China. Cytogenetic analyses including G-banding, chromosome painting and observation of synaptonemal complexes (SCs) demonstrated that the pregnancy wastage was associated with a balanced reciprocal translocation t(11;18) (q13.3; q23). The proband was the carrier of the translocation and his karyotype was 46,XY,t(11;18)(11pter-->11q13.3:: 18q23-->18qter; 18pter-->18q23::11q13.3-->11qter). The pedigree was analyzed based on a G-banded karyotype of the nine familial members. The translocation chromosomes came from the proband's mother. The result of the SC observation in the proband showed that each of the spermatocytes displayed one quadrivalent during their pachytene stages. In the quadrivalents, there existed homologous and nonhomologous synapses and the latter occurred widely during early, middle and late pachytene stages. The reasons and genetic basis of the pregnancy wastage are discussed.     

Clinical and molecular cytogenetic analysis of a rare case of mosaicism for partial monosomy 3p and partial trisomy 10q in human

The results of comprehensive clinical examination and molecular cytogenetic analysis of a patient carrying chromosome 3p+ in 69% of the peripheral blood lymphocytes are presented. Using microdissection of the metaphase chromosomes followed by DOP-PCR, a DNA library specific for the abnormal chromosome was obtained. By fluorescence in situ hybridization (FISH) of this DNA library with chromosomes from the patient and a healthy donor, the aberrant chromosome was identified as der(3)t(3;10)(3p25;q24.3). Since this chromosome was present in only a proportion of patient's cells studied and no chromosome aberrations were revealed in cells of his parents, the der(3)t(3;10) is suggested to appear de novo. The cells carrying der(3)t(3;10) are monosomic for a proportion of 3p25 and trisomic for 10q24.3-->qter. The developmental malformations revealed in the patient, such as the specific features of facial skeleton, mental retardation, microcephaly, and others are similar to those described previously in patients with partial 3p monosomy and 10q trisomy.     

The donor chromosome breakpoint for a jumping translocation is associated with large low-copy repeats in 21q21.3

Jumping translocations (JTs) are very rare chromosome aberrations, usually identified in tumors. We report a constitutional JT between donor chromosome 21q21.3-->qter and recipients 13qter and 18qter, resulting in an approximately 15.5-Mb proximal deletion 21q in a girl with mild developmental delay and minor dysmorphic features. Using fluorescence in situ hybridization (FISH) studies, we identified an approximately 550-kb complex inter- and intra-chromosomal low-copy repeat (LCR) adjacent to the 21q21.3 translocation breakpoint. On the recipient chromosomes 13qter and 18qter, the telomeric sequences TTAGGG were retained. Genotyping revealed that the deletion was of maternal origin. We propose that genome architecture involving LCRs may be a major mechanism responsible for the origin of jumping translocations.     

Inherited pericentric inversion of chromosome no. 2 with Robertsonian translocation (13q 14q) resulting in trisomy for chromosome 13q

This report includes a patient with an inherited pericentric inversion of chromosome No. 2 in addition to a Robertsonian translocation resulting in trisomy for chromosome 13q. The chromosomal constitution of the proband was 46,XX,inv(2) (pter leads to p11 : : q14 leads to p11 : : q14 leads to qter); t(13,14) (13qter leads to 13p11 : : 14q11 leads to 14qter). Sequential QFQ, RFA and GTG banding techniques were employed on the chromosomes of all family members. The chromosomal constitutions of the father and his first child were normal while the mother had an inversion of chromosome No. 2 [46,XX,inv(2) (pter leads to p11 : : q14 leads to p11 : : q14 leads to qter)]. The proband inherited this abnormal chromosome. In addition, she had a de novo Robertsonian translocation involving chromosomes 13q and 14q resulting in trisomy of chromosome 13q.