Trisomy 9p Research Articles

Partial trisomy and partial monosomy resulting from a reciprocal segregating in a large family

Partial trisomy 7p with partial monosomy 9p is a rare disorder with only 3 cases reported. Both these abnormalities i.e., partial trisomy 7p and partial monosomy 9p result in distinct clinical phenotypes. However, patients with combined 7p trisomy/9p monosomy present with a phenotype consistent with trisomy 7p. We present a fourth case of trisomy 7p/monosomy 9p with long term follow-up and document the medical complications associated with this disorder. Long term follow-up of patients with chromosome abnormalities provides a unique opportunity to document the medical history and complications associated with such abnormalities.

Corpus Callosum Agenesis in Trisomy 8p11.23 and Monosomy 4q34 Because of Maternal Translocation

We report on a 3-year-old boy with partial trisomy 8 p11.23-->pter and partial monosomy 4q34-->qter, associated with developmental delay, complete agenesis of the corpus callosum, and mild dysmorphic features. Although agenesis of the corpus callosum is not a rare finding among chromosomal abnormalities, partial trisomy 8p together with partial monosomy 4q, resulting from a maternal translocation, was not previously reported, to the best of our knowledge.

Cytogenetic studies of 24 renal epithelial tumors with von Hippel-Lindau and fragile histidine triad protein expression correlation.

Abstract Context.—Deletion of the short arm of chromosome 3 (3p deletion) is a cytogenetic abnormality generally associated with clear cell renal cell carcinoma, the most aggressive form of renal epithelial tumor. Objective.—To cytogenetically characterize 24 renal tumors in order to check the incidence and the type of 3p deletions, as well as to identify new genes putatively participating in renal tumorigenesis and test the protein products of the von Hippel-Lindau (VHL) and fragile histidine triad (FHIT) genes. Design.—We analyzed 24 renal tumors by conventional cytogenetics, comparative genomic hybridization, and fluorescence in situ hybridization. We then performed a comparative expression study of the proteins pVHL and Fhit. Results.—In our series of 24 renal tumors, the 3p deletion was the most frequent genetic alteration (15/24); the other features were partial trisomy 5q, 8p deletion, and monosomy 9 and 14. The 3p deletion was long and terminal, and no interstitial deletion was identified. By immu...

Cytogenetic Studies of 24 Renal Epithelial Tumors With von Hippel-Lindau and Fragile Histidine Triad Protein Expression Correlation

Deletion of the short arm of chromosome 3 (3p deletion) is a cytogenetic abnormality generally associated with clear cell renal cell carcinoma, the most aggressive form of renal epithelial tumor. To cytogenetically characterize 24 renal tumors in order to check the incidence and the type of 3p deletions, as well as to identify new genes putatively participating in renal tumorigenesis and test the protein products of the von Hippel-Lindau (VHL) and fragile histidine triad (FHIT) genes. We analyzed 24 renal tumors by conventional cytogenetics, comparative genomic hybridization, and fluorescence in situ hybridization. We then performed a comparative expression study of the proteins pVHL and Fhit. In our series of 24 renal tumors, the 3p deletion was the most frequent genetic alteration (15/24); the other features were partial trisomy 5q, 8p deletion, and monosomy 9 and 14. The 3p deletion was long and terminal, and no interstitial deletion was identified. By immunohistochemistry, we found that for the 2 genes of interest, VHL and FHIT, loss or decrease in protein expression were very frequently observed in clear cell renal cell carcinoma and not always associated with a 3p deletion (14/20 in clear cell renal cell carcinoma). Our studies characterize the 3p deletion as long and terminal and identify no interstitial deletion in that chromosome. Fhit and pVHL protein expression loss appear to be independent, as they can be dissociated. Our data are supportive of a role for FHIT (in addition to VHL) in renal tumorigenesis. No other gene with particular potential interest in renal tumorigenesis could be identified among the selected genes.

Prenatal diagnosis of concomitant Wolf–Hirschhorn syndrome and split hand‐foot malformation associated with partial monosomy 4p (4p16.1→pter) and partial trisomy 10q (10q25.1→qter)

Prenatal DiagnosisVolume 28, Issue 5 p. 450-453 Research Letter Prenatal diagnosis of concomitant Wolf–Hirschhorn syndrome and split hand-foot malformation associated with partial monosomy 4p (4p16.1→pter) and partial trisomy 10q (10q25.1→qter) Chih-Ping Chen, Corresponding Author Chih-Ping Chen [email protected] Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Department of Biotechnology, Asia University, Taichung, Taiwan School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, TaiwanDepartment of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei 104, Taiwan.Search for more papers by this authorYann-Jang Chen, Yann-Jang Chen Faculty of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan Department of Pediatrics, Veteran General Hospital, Taipei, TaiwanSearch for more papers by this authorSchu-Rern Chern, Schu-Rern Chern Department of Medical Research, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorFuu-Jen Tsai, Fuu-Jen Tsai Departments of Medical Genetics, and Medical Research, China Medical University Hospital, Taichung, TaiwanSearch for more papers by this authorTung-Yao Chang, Tung-Yao Chang Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorChen-Chi Lee, Chen-Chi Lee Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorDai-Dyi Town, Dai-Dyi Town Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorMeng-Shan Lee, Meng-Shan Lee Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorWayseen Wang, Wayseen Wang Department of Medical Research, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this author Chih-Ping Chen, Corresponding Author Chih-Ping Chen [email protected] Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Department of Biotechnology, Asia University, Taichung, Taiwan School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, TaiwanDepartment of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei 104, Taiwan.Search for more papers by this authorYann-Jang Chen, Yann-Jang Chen Faculty of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan Department of Pediatrics, Veteran General Hospital, Taipei, TaiwanSearch for more papers by this authorSchu-Rern Chern, Schu-Rern Chern Department of Medical Research, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorFuu-Jen Tsai, Fuu-Jen Tsai Departments of Medical Genetics, and Medical Research, China Medical University Hospital, Taichung, TaiwanSearch for more papers by this authorTung-Yao Chang, Tung-Yao Chang Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorChen-Chi Lee, Chen-Chi Lee Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorDai-Dyi Town, Dai-Dyi Town Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorMeng-Shan Lee, Meng-Shan Lee Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorWayseen Wang, Wayseen Wang Department of Medical Research, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this author First published: 08 April 2008 https://doi.org/10.1002/pd.1993Citations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume28, Issue5May 2008Pages 450-453 RelatedInformation

A Case of Partial Trisomy 9pter→q13 due to Paternal Balanced Translocation t (9;21) (q13;q21)

Trisomy 9p is one of the most frequent autosomal anomalies compatible with a long survival rate. Clinical characteristics are craniofacial dysmorphisms including hypertelorism, prominent nose, deepset eyes, and down-slanting palpebral fissures. The degree of clinical severity in trisomy 9 roughly correlates with the extent of trisomic chromosomal material. If the trisomic segments include the long arm of chromosome 9, clinical findings may not fit into the trisomy 9p but rather resemble trisomy 9 mosaic syndrome and are associated with muscular and cardiac anomalies. Therefore, breakpoints as well as clinical findings need to be precisely defined for differential diagnosis. Cases with trisomy 9p, especially involving proximal 9q, are very rare in Korea. The patient was a 1,920 g male infant born at 36 weeks 3 days of gestation to a 27-yr-old mother and 32-yr-old father after Cesarian section. The patient showed specific craniofacial anomalies, cardiac defects, and hand anomalies. Routine cytogenetic analysis, performed on peripheral blood using GTG banding, showed 46,XY,+der(9)t (9;21)(q13;q21),-21pat. Furthermore, FISH (Vysis Inc., USA) analysis with whole chromosome painting probes confirmed the derivative chromosome 9.

PACAP and its receptor VPAC1 regulate megakaryocyte maturation: therapeutic implications

Megakaryocytes and platelets express the Gs-coupled VPAC1 receptor, for which the pituitary adenylyl cyclase-activating peptide (PACAP) and the vasointestinal peptide (VIP) are agonists. We here demonstrate a regulatory role for VPAC1 signaling during megakaryopoiesis. A total of 2 patients with trisomy 18p with PACAP overexpression and transgenic mice overexpressing PACAP in megakaryocytes have thrombopathy, a mild thrombocytopenia, and a reduced number of mature megakaryocytes in their bone marrow. In vitro differentiation of hematopoietic stem cells from the patient and transgenic mice shows a reduced number of megakaryocyte colonies compared with controls. The addition of PACAP, VIP, or the adenylyl cyclase activator forskolin to CD34(+) cells inhibits megakaryocyte differentiation. In contrast, neutralizing monoclonal anti-PACAP (PP1A4) or anti-VPAC1 (23A11) antibodies inhibit cAMP formation and stimulate megakaryopoiesis in a thrombopoietin-independent manner. Moreover, wild-type mice obtain an increased platelet count after subcutaneous injection of PP1A4 or 23A11. These antibodies also elevate platelet numbers in animal models of myelosuppressive therapy and in GATA1-deficient mice with congenital thrombocytopenia. Furthermore, 23A11 stimulates the in vitro megakaryocyte differentiation of both normal and GATA1-deficient human CD34(+) cells. Together, our data strongly suggest that VPAC1 signaling tempers normal megakaryopoiesis, and that inhibition of this pathway stimulates megakaryocyte differentiation, enhancing platelet recovery after myelosuppressive therapy and in GATA1 deficiency.

Larsen‐like phenotype associated with partial trisomy 3p and monosomy 5p

We report on a fetus with radiographic features of Larsen Syndrome (LS) and unbalanced 3;5 translocation. Recently LS was shown to be caused by mutations in FLNB gene which maps on 3p14.3. Comparative genomic hybridization (CGH) was performed to search for genomic imbalances. Fluorescence in situ analysis (FISH) was done with BAC clone RP11-754F19 probe from the FLNB gene region (3p14.3). CGH showed a large loss of the chromosome 5 short arm and a gain of half of the short arm of chromosome 3 resulting from a derivative chromosome 5. FISH analysis with FLNB probe demonstrated that it was not triplicated. Thus, we excluded the role of a gene dosage effect of FLNB in abnormal craniofacial development in this fetus. To our knowledge, this is the first report of Larsen-like phenotype associated with unbalanced translocation resulting in partial trisomy 3p and monosomy 5p.

Multiple Ocular Abnormalities Associated with Trisomy 4p

Ocular features associated with trisomy 4p have rarely been described. The authors have experienced multiple ocular abnormalities (bilateral cataracts, posterior synechiae, and posterior segment changes) associated with this chromosomal abnormality. It was presumed that these intraocular findings might be associated with the previous inflammatory process. In the current case, the patient recovered some useful vision after surgical removal of cataracts and intraocular lens implantations in both eyes. A detailed ophthalmic examination for patients with the autosomal imbalance is recom-mended.

Partial monosomy Xq(Xq23 → qter) and trisomy 4p(4p15.33 → pter) in a woman with intractable focal epilepsy, borderline intellectual functioning, and dysmorphic features

Studies of epilepsy associated with chromosomal abnormalities may provide information about clinical and EEG phenotypes and possibly to identify new epilepsy genes. We describe a female patient with intractable focal epilepsy, borderline intellectual functioning, and facial dysmorphisms, in whom genetic study (i.e., karyotype and array-CGH analysis) revealed a distal trisomy 4p and distal monosomy Xq. Although any genetic hypothesis remains speculative, several genes are located in the 4p chromosome segment involved in the rearrangement, some of which may be related to epilepsy.

Concurrent transposition of distal 6p and 20q to the 22q telomere: A recurrent benign chromosomal variant

We report the second instance of a complex unbalanced rearrangement consisting of distal trisomy 6p and 20q due to the concurrent transposition of distal 6p and 20q to the 22q telomere, previously described as a benign familial chromosomal variant. In the previous case, the nonpathogenicity of the rearrangement was based on the absence of genotypic differences between the affected proband and his normal father, and on the absence of imprinted genes in the unbalanced region. We now describe the same variant in an unrelated affected subject, in whom testing confirmed the diagnosis of Angelman syndrome, and in his healthy father. Molecular investigations confirmed that the two families have an identical subtelomeric rearrangement. However, genotyping of the flanking sequences on 22q showed a completely different pattern in the two families, demonstrating that they are indeed unrelated. Array-CGH analysis with a resolution of ∼20 kb (Kit 244A, Agilent) defined a deletion size of 5.9 Mb on 15q11.2. No other imbalances were visible at subtelomeric regions. Further Array-CGH analysis using DNA of the proband (as test) and his mother (as reference) did not detect any duplication at the 6p and 20q subtelomeric regions. The proband and his father appear to have a copy number of the transposed regions equal to that of individuals with a normal repartition of the subtelomeric regions. This is not suggestive of a trisomy but rather of CNV regions. This type of rearrangement could define a new class of polymorphic variants, i.e. positional variants, as observed for pericentromeric heterochromatin.

Myelodysplastic Syndromes and Philadelphia Negative Chronic Myeloproliferative Diseases Show an Overlapping Pattern of Cytogenetic Aberrations.

The WHO classification introduced 3 categories:1.chronic myeloproliferative diseases (CMPD)2.myelodysplastic/myeloproliferative diseases (MDS/CMPD) and3.myelodysplastic syndromes (MDS).The aim was to analyze the pattern of cytogenetic aberrations in these categories excluding CML. In total 1996 cases belonging to these subgroups were referred to our laboratory and analyzed by chromosome banding analysis and cytomorphology. By cytomorphology 438 cases were classified as CMPD, 608 as MDS and 147 as MDS/CMPD. In 350 patients cytomorphology suspected a CMPD (CMPD-s) and in 423 a suspected MDS (MDS-s) but not all requested cytomorphologic criteria were fulfilled in these cases. Chromosome aberrations were detected in 81 of 438 CMPD (18.5%), 232 of 608 MDS (38.2%), 38 of 147 MDS/CMPD (25.9%), 33 of 350 CMPD-s (9.4%) and 71 of 423 MDS-s (16.8%). Therefore, 455 cases showing chromosome aberrations were identified and are the basis for aberration pattern analysis. In all three cytomorphologic categories balanced rearrangements were rare (n=40). The only recurring ones were 3q26-rearrangements (n=4). The most frequent aberrations were +1q (n=22), +8 (n=82, as the sole abnormality n=46), +9p (n=28) and +21 (n=16), i(17)(q10) (n=11), −7 (n=39, as the sole abnormality n=16), and loss of 5q (n=117), 5q deletion as the sole abnormality (n=45), 11q- (n=11), 12p- (n=21), 13q- (n=5), 20q- (n=59, as the sole abnormality n=41), and loss of the Y-chromosome (n=69). A complex aberrant karyotype (≥3 aberrations) was observed in 71 cases. None of these abnormalities was specific for one category. However, the following aberrations were significantly more frequently observed in CMPD as compared to MDS: +1q (10.6% vs 2.6%, p=0.001), +9p (23.0% vs. 0.3%, p<0.0001), +9 sole (8.8% vs. 0.0%. p<0.0001), and balanced rearrangements (15.0% vs. 6.3%. p=0.005). On the other hand the following aberrations were significantly more frequently observed in MDS as compared to CMPD: -Y (18.2% vs. 7.9%. p=0.01), deletion 5q (34.4% vs. 8.8%. p<0.0001), deletion 5q sole (13.9% vs. 2.7%. p=0.001), −7 (9.6% vs. 4.4%. p=0.04), complex aberrant karyotype (18.5% vs. 9.7%. p=0.03). A comparison of the frequencies of abnormalities between MDS/CMPD and CMPD and MDS, respectively, revealed that +8 as the sole abnormality and +21 were significantly more frequent in MDS/CMPD as compared to CMPD or MDS (+8 sole: 21.0% vs 6.2% vs 10.3%, p=0.008 and p=0.05, respectively; +21: 23.6% vs. 0.9% vs 3.3%, p=0.001 and p=0.005, respectively). Deletion 5q and 5q- as the sole abnormality was significantly more frequent in MDS as compared to CMPD/MDS (34.4% vs. 7.9%, p=0.001 and 13.9% vs 0%, p=0.014), while +9 as the sole abnormality was less frequently found in MDS compared to CMPD/MDS (0% vs 2.6%, p=0.005). Trisomy 9p was significantly more frequent in CMPD as compared to CMPD/MDS (23.6% vs. 2.6%, p=0.005), while monosomy 7 as the sole abnormality was less frequently found in CMPD as compared to CMPD/MDS (0.9% vs 7.9%, p=0.02). In conclusion, MDS and CMPD show an overlapping pattern of cytogenetic aberrations with aberrations such as +8, loss of 11q, 12p, 13q and 20q occurring with comparable frequencies. However, trisomy 1q and 9p were observed more frequently in CMPD while -Y, 5q deletion, monosomy 7 and complex aberrant karyotype were predominantly found in MDS. Also from the cytogenetic point of view CMPD/MDS cases are not distinguishable from either MDS or CMPD. However, +21 and +8 as the sole abnormality are more frequently observed in MDS/CMPD as compared to CMPD and MDS.

The Pallister-Killian syndrome in a child with rare karyotype—a diagnostic problem

The Pallister-Killian syndrome is a clinically recognizable syndrome, usually due to a tissue-specific mosaicism for a 12p isochromosome [i(12p)]. We report a rare case of Pallister-Killian syndrome with 12p mosaicism, tetrasomy/trisomy/disomy in fibroblasts and trisomy/disomy in lymphocytes. Marker chromosomes were investigated with conventional cytogenetic techniques and fluorescent in situ hybridisation (FISH). The karyotype was established as: mos47,XX,+12p/47,XX,+i(12p)/46,XX. The cytogenetic result of the extra mosaic 12p presented in lymphocytes suggested the diagnosis of trisomy 12p, although, in combination with clinical manifestations, the Pallister-Killian syndrome was considered and confirmed by the cytogenetic analysis of fibroblasts.

Small supernumerary chromosome marker generating complete and pure trisomy 18p, characterized by molecular cytogenetic techniques and review

Small supernumerary marker chromosomes (sSMC) have been described from all human chromosomes with different sizes and shapes. However, it is difficult to know the clinical manifestations associated with them, because such knowledge depends on the size, presence of euchromatic material, degree of mosaicism and/or uniparental disomy (UPD). Pure trisomy of the whole arm of chromosome 18 (18p), has been described in only a few cases and the general consensus is that there is a mild phenotypic effect. Here we report on a newborn male presenting with an atrial septal defect and a club foot. The high resolution G-band karyotype (550-850 bands) and the molecular cytogenetic techniques revealed in all cells the presence of an sSMC, which was a complex derivative from the short arm of a chromosome 18 (18p) and a centromere of a chromosome 13/21. His healthy mother had the same sSMC in all analyzed cells. With the present case, we support the previous suggestion that this unusual chromosome trisomy 18p has little clinical repercussions.

A patient with an interstitial duplication of chromosome 5p11–p13.3 further confirming a critical region for 5p duplication syndrome

Partial or complete trisomy 5p has been associated with characteristic facial features, developmental delay, seizures, congenital heart defects, and respiratory compromise. We present a child with developmental delay, seizures, and congenital cardiac anomalies found to have a previously unreported de novo interstitial duplication of chromosome 5p, 46,XX,dup(5) (p11p13.3). The breakpoints of the duplication were further confirmed by fluorescence in situ hybridization analysis using bacterial artificial chromosome probes specific for the affected region. Comparison with previously reported cases of patients with duplications of 5p suggests loci of interest for both congenital heart anomalies and seizures.

Familial whole-arm translocations (1;19), (9;13), and (12;21): a review of 101 constitutional exchanges

We report here on 3 familial whole-arm translocations (WATs), namely the 8th instance of t(1;19)(p10;q10) and 2 novel exchanges: t(9;13)(p10;q10) and t(12;21)(p10;q10). The exchanges (1;19) and (12;21) were ascertained through a balanced carrier, whereas the t(9;13) was first diagnosed in a boy with a trisomy 9p syndrome and der(9p13p). Results of FISH analyses with the appropriate ?-satellite probes were as follows. Family 1, t(1;19): the D1Z5 probe gave a strong signal on both the normal chromosome 1 and the der(1q19p) as well as a weak signal on the der(1p19q). Family 2, t(9;13): the centromere-9 alphoid and D13Z1/D21Z1 probes under standard stringency gave no signal on the der(9p13p) in both the proband and a carrier brother, whereas the der(9q13q) was labelled only with the centromere-9 alphoid repeat in the latter; yet, this probe under low stringency revealed a residual amount of alphoid DNA on the der(9p13p) in the carrier. Family 3, t(12;21): the D12Z3 probe gave a signal on the normal chromosome 12 and the der(12p21q), whereas the D13Z1/D21Z1 repeat labelled the der(12q21p), the normal chromosome 21, and both chromosomes 13. Out of 101 WATs compiled here, 73 are distinct exchanges, including 32 instances between chromosomes with common alphoid repeats. Moreover, 7/9 of recurrent WATs involved chromosomes from the same alphoid family. Thus constitutional WATs appear to recur more frequently than other reciprocal exchanges, often involve chromosomes with common alphoid repeats, and can mostly be accounted for the great homology in alphoid DNA that favours mispairing and illegitimate nonhomologous recombination.

Partial Trisomy 3p and Monosomy 7p Associated with Tetralogy of Fallot and Infantile Seizure

A 7-month-old female infant was referred because of hypothyroidism, seizure, respiratory distress syndrome, and tetralogy of Fallot (TOF) with hypoxic spell. Her father and 24-year-old mother were healthy and nonconsanguineous. There was no family history of congenital malformations. The mother denied any exposure to alcohol, teratogenic agents or infectious diseases during this pregnancy. She received regular prenatal examinations at a local clinic. The infant was born prematurely at 35 weeks of gestation. However, bradycardia, restlessness, cyanosis, gasping respiration, upgaze, and episodes of seizure developed soon after delivery. The infant’s external appearance was grossly normal, and the extremities were freely movable. The body weight was less than third percentile with growth restriction. Serial studies were arranged. Echocardiography revealed an atrial septal defect, a large ventricular septal defect, right ventricular hypertrophy, and severe pulmonary stenosis that were consistent with TOF. Brain sonography revealed moderate dilatation of lateral and third ventricles, in favor of the diagnosis of benign extracerebral fluid collection. Conventional cytogenetic studies performed on the

Bilateral Semilunar Valve Dysplasia in a Patient with Inverted Duplication 2p25–22

Here we report a patient with partial trisomy 2p and congenital dysplasia of the semilunar valves. To our knowledge, this is the first case of 2p duplication with developmental defects of both semilunar valves and suggests that genes on this region contribute to the formation of the semilunar valves.

A case of de novo partial tetrasomy of distal 6p and review of the literature

We report on a 3-year-old girl with bilateral eyelid colobomas, bulbous nose, blepharophimosis, blepharoptosis, sensorineural hearing loss, atrial septal defect, psychomotor retardation, and growth delay. Cytogenetic analysis showed additional material of unknown origin on the short arm of chromosome 8. Whole chromosome paint FISH identified the additional material to originate from chromosome 6. Subtelomeric metaphase FISH analysis detected a bright signal pattern for the 6p subtelomere probe on the derivative 8 as well as two short arm signals for the normal chromosomes 6. Interphase FISH with the 6p subtelomere probe demonstrated four 6p signals. Interestingly, metaphase FISH with a probe for the 8p subtelomere region demonstrated a signal for 8p just proximal to the translocated material. Comparative genomic hybridization studies confirmed tetrasomy of the 6p subtelomere region from 6p25.1 --> 6p25.3. Thus our patient represents the first reported case of "pure" partial tetrasomy 6p, meaning the tetrasomy was not associated with a significant deletion of chromosome arm 8p. We compare here this case with previously reported cases of partial trisomy 6p and the resulting phenotypes.

Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Small supernumerary marker chromosomes (sSMCs) are a morphologically heterogeneous group of additional structurally abnormal chromosomes that cannot be identified unambiguously by conventional banding techniques alone. Molecular cytogenetic methods enable detailed characterization of sSMCs; however, in many cases interpretation of their clinical significance is problematic. The aim of our study was to characterize precisely sSMCs identified in three patients with dysmorphic features, psychomotor retardation and multiple congenital anomalies. We also attempted to correlate the patients' genotypes with phenotypes by inclusion of data from the literature. The sSMCs were initially detected by G-banding analysis in peripheral blood lymphocytes in these patients and were subsequently characterized using multicolor fluorescence in situ hybridization (M-FISH), (sub)centromere-specific multicolor FISH (cenM-FISH, subcenM-FISH), and multicolor banding (MCB) techniques. Additionally, the sSMCs in two patients were also studied by hybridization to whole-genome bacterial artificial chromosome (BAC) arrays (array-CGH) to map the breakpoints on a single BAC clone level. In all three patients, the chromosome origin, structure, and euchromatin content of the sSMCs were determined. In patient RS, only a neocentric r(2)(q35q36) was identified. It is a second neocentric sSMC(2) in the literature and the first marker chromosome derived from the terminal part of 2q. In the other two patients, two sSMCs were found, as M-FISH detected additional sSMCs that could not be characterized in G-banding analysis. In patient MK, each of four cell lines contained der(4)(:p11.1-->q12:) accompanied by a sSMC(18): r(18)(:p11.2-->q11.1::p11.2-->q11.1:), inv dup(18)(:p11.1-->q11.1::q11.1-->p11.1:), or der(18) (:p11.2-->q11.1::q11.1-->p11.1:). In patient NP, with clinical features of trisomy 8p, three sSMCs were characterized: r(8)(:p12-->q11.1::q11.1-->p21:) der(8) (:p11.22-->q11.1::q11.1-->p21::p21-->p11.22:) and der(21)(:p11.1-->q21.3:). The BAC array results confirmed the molecular cytogenetic results and refined the breakpoints to the single BAC clone resolution. However, the complex mosaic structure of the marker chromosomes derived from chromosomes 8 and 18 could only be identified by molecular cytogenetic methods. This study confirms the usefulness of multicolor FISH combined with whole-genome arrays for comprehensive analyses of marker chromosomes.