Partial trisomy 18q11.2-->qter due to de novo unbalanced translocation of chromosomes 15 and 18 analyzed by fluorescence in situ hybridization

This report presents a case with partial trisomy 18q resulting from de novo unbalanced translocation of chromosomes 15 and 18 displaying the features of pure trisomy. This is the first reported case with partial trisomy 18q due to unbalanced translocation between chromosomes 15 and 18. Clinical findings of our case have been compared with the reported cases' had partial trisomy 18q and the importance to recognize the cases with chromosome abnormalities to give genetic counseling and prenatal diagnosis for subsequent pregnancies has emphasized.     

Unbalanced 1q whole-arm translocation resulting in der(14)t(1;14)(q11-12;p11) in myelodysplastic syndrome

Unbalanced whole-arm translocations (WATs) of the long arm of chromosome 1, resulting in complete trisomy 1q, are chromosomal abnormalities detectable in both solid tumors and hematologic neoplasms. Among the WATs of 1q to acrocentric chromosomes, a few patients with der(1;15) described as a dicentric chromosome have been reported so far, whereas cases of der(1;14) are much rarer. We report on a case of der(1;14) detected as single anomaly in a patient with myelodysplastic syndrome. The aim of our work was to investigate the breakpoints of the (1;14) translocation leading to the der(1;14). Fluorescence in situ hybridization (FISH) experiments have been performed on chromosome preparations from bone marrow aspirate, using specific centromeric probes of both chromosomes, as well as a probe mapping to 1q11 band. FISH results showed that in our patient the derivative chromosome was monocentric with a unique centromere derived from chromosome 14. The breakpoints of the translocation were located in the short arm of chromosome 14 and in the long arm of chromosome 1, between the alphoid D1Z5 and the satellite II domains. The 1q breakpoint was within the pericentromeric region of chromosome 1, which is notoriously an unstable chromosomal region, involved in different chromosomal rearrangements.     

46,XX, der(15),t(Y;15)(q12;p11) karyotype in an azoospermic male

We report on a Yq/15p translocation in a 23-year-old infertile male referred for Klinefelter Syndrome testing, who had azoospermia and bilateral small testes. Hormonal studies revealed hypergonadotropic hypogonadism. Conventional cytogenetic procedures giemsa trypsin giemsa (GTG) and high resolution banding (HRB) and molecular cytogenetic techniques Fluorescence In Situ Hybridization (FISH) performed on high-resolution lymphocyte chromosomes revealed the karyotype 46,XX, t(Y;15)(q12;p11). SRY-gene was confirmed to be present by classical Polymerase Chain Reaction (PCR) methods. His father carried de novo derivative chromosome 15 [45,X, t(Y;15)(q12;p11)] and was fertile; the karyotype of the father using G-band technique confirmed a reciprocal balanced translocation between chromosome Y and 15. In the proband, the der (15) has been inherited from the father because the mother had a normal karyotype (46,XX). In the proband, the der (15) could have produced genetic imbalance leading to unbalanced robertson translocation between chromosome Y and 15, which might have resulted in azoospermia and infertility in the proband. The paternal translocation might have lead to formation of imbalanced ova, which might be resulted infertility in the proband. Sister''s karyotypes was normal (46,XX) while his brother was not analyzed.     

Tertiary trisomy of 10p15.pter and 14pter.ql3 due to maternal translocation t(10;14)(p15;q13)

Double partial trisomy resulting from 3:1 segregation of the respective chromosomal segments of the chromosomes involved in a balanced translocation in meiosis is rarely reported in the literature. We present here a first patient with multiple congenital malformations associated with double partial trisomy of 10pter-p15 and 14pter-q13 resulting from 3:1 segregation of maternal balanced translocation t(10;14)(p15;q13). Proximal partial trisomy of chromosome 14 and subterminal trisomy of the short arm of the chromosome 10 are rare. The present case is the first case with double partial trisomy of these segments resulting from 3:1 segregation of a maternal balanced translocation.     

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.     

A rare case of aniridia and balanced translocation (5;11) (p15.3;q22) arising in the same subject: a challenge for genetic counseling

The authors report on a case of isolated aniridia caused by haploinsufficiency of the PAX6 gene, which is located on 11p13, and a balanced translocation t(5;l1)(p15.3;q22) inherited respectively from his father and his mother. Due to the coincidence of two abnormalities in the same chromosome, the segregation of the mutant allele leading to aniridia and of the chromosomes involved in the translocation are not independent events. Considering that both monosomy and trisomy for 11q22-qter are unviable, his offspring may inherit either the PAX6 mutation or the balanced translocation. However, depending on the occurrence of crossing over, there is a possibility for him to have normal offspring; on the other hand, he may also father children with both anomalies. This unusual case, in which the proband has a presumably very low chance of completely normal offspring, turned to be a challenge for genetic counseling.     

Report of a patient with a trisomy of chromosome region 20q11.2-->20q12 and characterization with FISH

We report on a 16-month-old boy presenting with psychomotor retardation, craniofacial anomalies and severe vision deficit. Analysis of GTG-banded chromosomes showed that the patient had extra chromosomal material in the long arm of one chromosome 20. This chromosome aberration was further characterized with FISH using a chromosome 20 specific paint and band-specific probes. A partial trisomy 20q was shown to be present, the karyotype being 46, XY, dup (20) (q11.2q12). The cytogenetic and clinical findings are compared with cases previously reported in the literature.     

Distal monosomy 16p13.3/distal trisomy 2p24.2-pter: molecular-cytogenetic characterisation and phenotype

We describe a 4-year-old boy with various facial dysmorphic features such as downslanting palpebral fissures, ptosis, hypertelorism, broad nasal bridge, small and low-set ears, broad philtrum, and micrognathia. In addition, profound mental retardation, myopia, muscular hypotonia as well as genital and cardiovascular abnormalities are also present. Refinement of the breakpoints by cytogenetic techniques, in particular the increase of banding resolution in conventional cytogenetic analysis, has enabled the correct diagnosis, as proven by fluorescence in situ hybridisation (FISH) using whole chromosome painting and single copy probes. We were able to demonstrate an unbalanced translocation that the patient inherited from his father resulting in a submicroscopic monosomy 16p13.3 and a trisomy 2p24.2-pter.     

Molecular cytogenetic characterization of 17 rob(13q14q) Robertsonian translocations by FISH, narrowing the region containing the breakpoints.

We have characterized 17 rob(13q14q) Robertsonian translocations, using six molecular probes that hybridize to the repetitive sequences of the centromeric and shortarm regions of the five acrocentric chromosomes by FISH. The rearrangements include six de novo rearrangements and the chromosomally normal parents, five maternally and three paternally inherited translocations, and three translocations of unknown origin. The D21Z1/D13Z1 and D14Z1/D22Z1 centromeric alpha-satellite DNA probes showed all rob(13q14q) chromosomes to be dicentric. The rDNA probes did not show hybridization on any of the 17 cases studied. The pTRS-47 satellite III DNA probe specific for chromosomes 14 and 22 was retained around the breakpoints in all cases. However, the pTRS-63 satellite III DNA probe specific for chromosome 14 did not show any signals on the translocation chromosomes examined. In 16 of 17 translocations studied, strong hybridization signals on the translocations were detected with the pTRI-6 satellite I DNA probe specific for chromosome 13. All parents of the six de novo rob(13q14q), including one whose pTRI-6 sequence was lost, showed strong positive hybridization signals on each pair of chromosomes 14 and 13, with pTRS-47, pTRS-63, and pTRI-6. Therefore, the translocation breakpoints in the majority of rob(13q14q) are between the pTRS-47 and pTRS-63 sequences in the p11 region of chromosome 14 and between the pTRI-6 and rDNA sequences within the p11 region of chromosome 13.     

A family with segregation of an unbalanced translocation (7;13) (q36;q32) in three patients with severe mental retardation, microcephaly and dysmorphic features, detected by subtelomere FISH: genetic counselling and prenatal diagnosis

We report a Sardinian family in which three members showed a mental-retardation-microcephaly-multiple malformations syndrome resulting from an unbalanced translocation (7;13)(q36;q32) which led to subtelomeric trisomy 7q36qter and partial monosomy 13q32qter. The unbalanced translocation was transmitted by alternate segregation from a female and a male carriers of the balanced translocation. The three patients had severe mental retardation, microcephaly and multiple minor facial and fingers anomalies. Neuroimages showed brain atrophy, associated in two patients with partial agenesis of the corpus callosum. FISH with chromosome 13 and 7 specific painting probes and subtelomere specific probes was instrumental for defining and characterizing the chromosomal translocation. Extensive genetic counseling and prenatal diagnosis has been offered to all the members of the family.     

Trisomy of medial 15q as result of an analphoid supernumerary ring chromosome detected by CGH and FISH

We report a 21-year-old patient with a de novo mosaic, analphoid ring of chromosome 15q22.2-->q24.1. The clinical features of this patient are mild and include tall stature, obesity, striae distensae in the hypogastrium, malocclusion and bilateral gynecomastia with scarce glandular tissue. M-FISH and FISH using a chromosome 15 painting probe indicated that the ring is of chromosome 15 origin. Further CGH analysis and FISH with the PML locus-specific probe demonstrated that the extra material derived from the medial part of the long arm of chromosome 15, including two bands, q22 and q23. Additionally, FISH with BAC probes specific for 15q allowed for a localization of the breakpoints at 15q22.2 and 15q24.1, distal to clones RP11-30M4 and RP11-500O23 respectively. We discuss the relationship between the patient's genotype and phenotype comparing it to reported cases of trisomy of medial 15q.     

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.     

Additional chromosome in a child as a result of a balanced reciprocal translocation t(12;18)(p13;q12) in his mother's karyotype

In this case report we present a child with an additional chromosome in the karyotype. The karyotypes of the boy and his parents were analyzed by use of a conventional banding technique (GTG) and fluorescence in situ hybridization (FISH). Probes painting whole chromosomes 12 and 18 were used in FISH. Cytogenetic examination of the parents revealed that his mother was carrying balanced reciprocal translocation between chromosomes 12 and 18. Her karyotype was described as 46,XX,t(12;18)(p13;q12). Father's karyotype was normal, described as 46,XY. The boy's karyotype was defined as 47,XY,+der(18)t(12;18)(p13;q12). The additional chromosome appeared probably due to 3:1 meiotic disjunction of the maternal balanced translocation, known as tertiary trisomy. The mother displayed a normal phenotype and delivered earlier a healthy child. However, the boy with the unbalanced karyotype shows multiple congenital abnormalities.     

A familial "balanced" 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings.

A child with phenotypic features of the 9p- syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, as well as hypopigmentation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his phenotypically normal father. Molecular analysis showed heterozygous deletion of the TYRP (tyrosinase-related protein) locus, as well as loci D9S157, D9S274, D9S268, and D9S267, in the child but in neither parent. FISH analysis of the proband''s father indicated that loci deleted in his son, including TYRP, were present on neither the der(3) nor the der(9) translocation products but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father''s 3;9 translocation chromosomes together with his normal chromosome 8 (not bearing the insertion from 9p23). Neither the deletion of these 9p23 loci from the translocation chromosomes nor their insertion into 8q was detectable by standard chromosome banding techniques. The proband''s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis showed that she had inherited normal chromosomes 3 and 9, as well as the chromosome 8 with the insertion of 9p23 material, from her father.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Partial trisomy 15q1

Summary A supernumerary extra chromosome of maternal origin, precisely described from QM- and C-banding patterns, was studied in a mentally defective boy with a severe convulsive disorder. This case is considered to represent a specific phenotype of trisomy 15q1. The suggestion that in cases of partial trisomy 15q different phenotypes are due to the second chromosome involved in interchange is supported by the observation of a tertiary trisomy in 2 sibs. It resulted from a balanced reciprocal translocation in the mother t(8q+15q-) and caused an unusual malformation syndrome (mental deficiency, cleft lip and palate, funnel chest, hypospadias).     

Proof of partial imbalances 6q and 11q due to maternal complex balanced translocation analyzed by microdissection of multicolor labeled chromosomes (FISH-MD) in a patient with Dandy-Walker variant

We report on a family in which a daughter is described with mental retardation, as well as malformations of the heart, and of the brain (Dandy-Walker variant). The patient's phenotype suggests a chromosomal rearrangement. However, her karyotype was unremarkable by conventional cytogenetic analysis. In order to detect chromosome rearrangements overseen by this method, the subtelomere regions of suspicious chromosomes were verified by fluorescence in situ hybridization (FISH). A rearranged derivative chromosome 6 was identified. Further examinations by FISH-microdissection (FISH-MD) revealed a maternal complex balanced translocation. The patient inherited the derivative chromosome 6 from her mother and therefore carries a partial monosomy 6q26-->qter and a partial trisomy 11q23.3-->qter.     

Partial trisomy 14q due to maternal t(4;14)(p16;q32) in a dysmorphic newborn

Partial Trisomy 14q is a rare chromosomal disorder that mostly results from a parental translocation. We report here a newborn boy with partial trisomy 14q and dysmorphic features that are compatible with previously reported cases. Conventional cytogenetic analysis revealed an extra chromosomal segment at the end of the short arm of chromosome 4. In order to determine the origin of this chromosome region we used subtelomeric FISH technique. Based on the results of these cytogenetic studies and the physical examination, this dysmorphic case was diagnosed as partial trisomy of 14q and his karyotype determined as 46 XY, der(4)t(4;14)(p16;q32) resulting from a balanced maternal translocation identified as 46,XX, t(4;14)(p16;q32).     

Uniparental heterodisomy for chromosome 14 in a phenotypically abnormal familial balanced 13/14 Robertsonian translocation carrier.

A 9-year-old mentally retarded girl with multiple congenital anomalies was found to carry a balanced 13/14 Robertsonian translocation [45,XX,t(13q14q)] which was also present in her father. Her mother carried a balanced reciprocal translocation between chromosomes 1 and 14 [46,XX,t(1;14) (q32;q32)]. Both of her parents were phenotypically normal. Molecular studies were carried out to determine the parental origin of chromosomes 1, 13, and 14 in the patient. Using probes for D14S13 and D14S22, we could show that the patient inherited both chromosomes 14 from her father and none from her mother. Similar studies using probes for chromosomes 1 (D1S76) and 13 (D13S37) loci showed the presence of both maternal and paternal alleles in the patient. Our findings indicate that paternal uniparental heterodisomy for chromosome 14 most likely accounts for the phenotypic abnormalities observed in our patient. It is suggested that uniparental disomy may be the basis for abnormal development in at least some phenotypically abnormal familial balanced-translocation carriers.     

The cytogenetics of 90 patients with idiopathic mental retardation/malformation syndromes and of 90 normal subjects

Summary A cytogenetic study, done on randomized coded slides, of 90 patients with idiopathic mental retardation and at least 3 other developmentally independent congenital anomalies and of 90 normal subjects is reported. Audiatorography, Q-banding and C-staining were used in the analysis of chromosomally abnormal cases. Eight patients were found to have chromosome abnormalities. Four had substantial chromosome aberrations that would be expected to cause abnormal phenotype. These were CD165 (46,18q-); CD25 (46,18q+) (partial trisomy of 10q); CD175 (46,4q+) and CD95 (46,mar22). In addition, 4 patients were found to have chromosomal anomalies that could not account for their conditions. Three of these were considered to have heterochromatic variants. Patient CD167 had an 9qh+ chromosome which had been inherited from her mother. Case CD137 had a No. 19 chromosome with additional centric heterochromatin. A similar chromosome was found in her mother, maternal grandmother and 2 of 3 half sibs. In patient CD125 a telocentric No. 13 was found. In addition, CD80 was shown to have an XYY constitution.In the normal subjects, no unbalanced chromosome rearrangements were found. Four persons, however, had minor chromosome anomalies. Three were considered to have heterochromatic variants. These were CD54 (46,22p+); CD149 (46,21p+) and CD19 (46,tel22). One normal subject (CD51) was found to be a balanced t(13q14q) carrier. The translocation chromosome had been inherited from his father.