Partial 1q Research Articles

Protein and mRNA Expression in Uveal Melanoma Cell Lines Are Related to GNA and BAP1 Mutation Status.

Cell lines are being used in preclinical uveal melanoma (UM) research. Because not all cell lines harbor typical GNAQ or GNA11 hotspot mutations, we aimed at better classifying them and determining whether we could find genetic causes to explain the protein and mRNA expression profiles of the cell lines. We studied protein and mRNA expression of 14 UM cell lines and determined the presence of single nucleotide variants and small insertions and deletions with next-generation sequencing and copy number alterations with a single nucleotide polymorphism array. The lists of differentially expressed proteins and genes were merged, and shared lists were created, keeping only terms with concordant mRNA and protein expression. Enrichment analyses were performed on the shared lists. Cell lines Mel285 and Mel290 are separate from GNA-mutated cell lines and show downregulation of melanosome-related markers. Both lack typical UM mutations but each harbors four putatively deleterious variants in CTNNB1, PPP1R10, LIMCH1, and APC in Mel285 and ARID1A, PPP1R10, SPG11, and RNF43 in Mel290. The upregulated terms in Mel285 and Mel290 did not point to a convincing alternative origin. Mel285 shows loss of chromosomes 1p, 3p, partial 3q, 6, and partial 8p, whereas Mel290 shows loss of 1p and 6. Expression in the other 12 cell lines was related to BAP1 expression. Although Mel285 and Mel290 have copy number alterations that fit UM, multi-omics analyses show that they belong to a separate group compared to the other analyzed UM cell lines. Therefore, they may not be representative models to test potential therapeutic targets for UM.

New insights on partial trisomy 3q syndrome: de novo 3q27.1-q29 duplication in a newborn with pre and postnatal overgrowth and assisted reproductive conception

BackgroundDuplications of the long arm of chromosome 3 are rare, and associated to a well-defined contiguous gene syndrome known as partial trisomy 3q syndrome. It has been first described in 1966 by Falek et al., and since then around 100 patients have been reported. Clinical manifestations include characteristic facial dysmorphic features, microcephaly, hirsutism, congenital heart disease, genitourinary anomalies, hand and feet abnormalities, growth disturbances and intellectual disability. Most of cases are due to unbalanced translocations, inherited from a parent carrying a balanced aberration (reciprocal translocation or inversion), and rarely the genomic anomaly arises de novo. Very few studies report on the prenatal identification of such rearrangements.Case presentationHereby, we report on a newborn with a rare pure duplication of the long arm of chromosome 3. Noninvasive prenatal test (cell free fetal DNA analysis on maternal blood), performed for advanced parental age and use of assisted reproductive technique, evidenced a partial 3q trisomy. Then, invasive cytogenetic (standard and molecular) investigations, carried out through amniocentesis, confirmed and defined a 3q27.1-q29 duplication spanning 10.9 Mb, and including about 80 genes. Our patient showed clinical findings (typical facial dysmorphic features, esotropia, short neck, atrial septal defect, hepatomegaly, mild motor delay) compatible with partial trisomy 3q syndrome diagnosis, in addition to pre- and postnatal overgrowth.ConclusionsAdvanced parental age increases the probability of chromosomal and/or genomic anomalies, while ART that of epigenomic defects. Both conditions, thus, deserve more careful prenatal monitoring and screening/diagnostic investigations. Among the latter, cell free fetal DNA testing can detect large segmental aneuploidies, along with chromosomal abnormalities. It identified in our patient a wide 3q rearrangement, then confirmed and defined through invasive molecular cytogenetic analysis. Neonatologists and pediatricians must be aware of the potential risks associated to duplication syndromes. Therefore, they should offer to affected subjects an adequate management and early and careful follow-up. These may be able to guarantee to patients satisfactory growth and development profiles, prevent and/or limit neurodevelopmental disorders, and timely recognition of complications.

Identification of partial trisomy 13q in two unrelated patients using single-nucleotide polymorphism array and literature overview

BackgroundPartial trisomy 13q is a less common chromosomal abnormality with a great clinical variability, among them, isolated partial trisomy 13q is extremely rare. Here, we report two new unrelated cases of partial trisomy 13q in Chinese families aiming to emphasize the genotype–phenotype correlation in partial trisomy 13q.MethodsEnrolled in this study were two unrelated cases of partial 13q trisomy from two families in Quanzhou region South China. Karyotpe and single-nucleotide polymorphism (SNP) array analysis were employed to identify chromosome abnormalities and copy number variants in the families.ResultsA 72.9-Mb duplication in 13q14.11q34 region was identified using SNP array analysis in Patient 1 with an intellectual disability, developmental delay, seizures, gastric perforation, and other congenital malformations from a family with paternal inv(13)(p12q14.1). SNP array detection in Patient 2 revealed a 92.4-Mb duplication in 13q12.11q34 region combined with an 8.4-Mb deletion in Xq27.3q28 region with intellectual disability, developmental delay, cleft palate, and duplication of the cervix and the vagina. No chromosomal abnormality was elicited from the parents of Patient 2.ConclusionsIn this study, we presented two new unrelated cases of partial trisomy 13q with variable features in Chinese population, which may enrich the spectrum of the phenotypes partial trisomy 13q and further confirm the genotype–phenotype correlation.

Interphase FISH Analysis Reveals High Frequence of Partial 6q Deletions in Adult Acute Lymphoblastic Leukemia (ALL) with Normal or Failed Karyotype.

Karyotypic analysis in adult ALL has provided relevant insights in the prognostic significance of chromosome abnormalities, which in turn become of potential importance for the design of risk-adapted therapeutic strategies for newly diagnosed cases. Among structural karyotypic changes, partial deletions of the long arm of chromosome 6 (6q) are reported to be between 4 and 6% of cases of adult ALL by conventional cytogenetics and depict a subset of patients with strict correlation with T-lineage ALL and an unfavorable prognostic likelihood. Recent studies at the molecular level in childhood ALL have shown 6q deletions in up to 30% of the investigated cases. With the aim of more precisely defining the exact incidence of 6q deletions in adult ALL, we started to investigate by interphase FISH patients with normal or failed karyotype included in the GIMEMA 0496 and 2000 protocols. These trials contemplated a central handling of bone marrow samples of the enrolled patients at presentation. We identified the following bacteria-derived artificial chromosome (BAC) clones with a known map location within the most common deleted region of 6q: 90G9 (6q13), 12B13 (6q15), 465M14 (6q21), 81H16 (6q26), 91016 (6q27). BAC clones were obtained from the Children's Hospital Oakland Research Institute (CHORI).Twenty-seven consecutive ALL patients have so far been analyzed by interphase FISH, 16 with T- and 11 with B-cell phenotype. Eleven cases had a normal karyotype and 16 a failed cytogenetic analysis. Among the cases with normal karyotype, 2 cases with T-cell phenotype showed a deletion in the 6q21 and 6q15 regions, whereas in the group with failed cytogenetics 1 case with B- and 3 cases with T-cell phenotype harbored deletions spanning respectively the 6q13-15 (2), 6q13-q21 and 6q15-21 regions. The median percentage of nuclei with 6q deletion was 30% (range 7–75%). T-ALL deleted cases showed the absence of the most frequent fusion genes detectable with molecular analysis, whereas a BCR-ABL rearrangement was identified in the only B-lineage ALL deleted case. Overall, partial 6q deletions were observed in 22% of the cases analyzed and in 31% of cases with T-cell phenotype. The present study shows that the probe set we have utilized is a useful tool for providing accurate cytogenetic diagnosis of partial 6q deletions and indicates that this abnormality is a frequent karyotypic change in adult ALL, particularly in T-lineage cases where it appears to represent the most relevant genetic anomaly. Since this abnormality is underestimated by conventional cytogenetic analysis, interphase FISH for 6q deletions should be included in the routine genetic screening of the ALL patients with failed or normal cytogenetics

Genetic analysis of a case with Pierre-Robin sequence due to partial 1q trisomy and partial 4q monosomy

To explore the genetic basis for a neonate with Pierre-Robin sequence. The child was subjected to chromosomal karyotyping, single nucleotide polymorphism array (SNP-array)-based comparative genomic hybridization and fluorescence in situ hybridization (FISH) analysis. The child has featured microgthnia, glossoptosis, upper airway obstruction, mandible dehiscence and short neck. He was found to have a karyotype of 46,XY,der(4)add(4)(q34). Her mother's karyotype was determined as 46,XX,t(1;4)(q43;q34), while his father was 46,XY. SNP-array analysis suggested the child to be arr [hg19] 1q42.2q44 (232 527 958-249 202 755)× 3; 4q34.3q35.2 (168 236 901-190 880 409)× 1. The result of SNP-array for both parents was normal. FISH analysis confirmed that his mother has carried a balanced t(1;4)(q42;34) translocation. The aberrant chromosome 4 in the child has derived from his mother's translocation, which gave rise to partial 1q trisomy and 4q monosomy. The 1q42.2q44 duplication and 4q34.3q35.2 deletion of the child probably underlay his abnormal phenotype of Pierre-Robin sequence.

Isochromosome 11q is Associated with Unique Characteristics and Poor Prognosis in Patients with Acute Myeloid Leukemia.

Isochromosome 11q in patients with acute myeloid leukemia is rarely reported, and little is known about its main features. The presence of isochromosome 11q was identified in four patients (three adults and one child) from screening 441 patients with an acute myeloid leukemia diagnosis between 2009 and 2018 by using R-banding and fluorescence in situ hybridization. The child, patient 1 with unreported isochromosome (partial 11q isochromosome), accompanied with t(1;11) translocation, initially achieved remission after receiving chemotherapy. However, 4 months later this patient experienced a relapse. While multiple treatments were tried, it had no effect and the patient survived for 16 months. The remaining patients with isochromosome 11q exhibited numerical/structural chromosomal abnormal-ities involving myelodysplastic syndrome-related chromosomes 5, 7, 8, and 20. In patients 2 and 3, we found a derivative chromosome 21. Patient 3 was newly diagnosed with acute myeloid leukemia and was treated with many chemotherapy protocols, unfortunately with no effect. The patient then received traditional Chinese medicine and survived for 10 months, although she still has not achieved complete remission. Patients 2 and 4 received chemotherapy but experienced rapid disease progression and died within 2 months. In summary, patients with isochromosome 11q/partial 11q isochromosome have a poorer prognosis, especially for isochromosome 11q. Furthermore, these chromosome aberrations may be risk factors for the presence of isochromosome 11q or myelodysplastic syndrome-related genes, both of them may be associated with a failure to respond to treatment and poor outcomes. Hence, these discoveries may lay a foundation to study mechanisms and explore treatments.

Prenatal identification of partial 3q duplication syndrome

BackgroundThe 3q duplication syndrome is a result of duplication of a large fragment of the long arm of chromosome 3, mainly 3q21-qter, and in most cases it is diagnosed only after birth. The phenotypic consequences resulting from genetic imbalance are an important source of information for genetic counselling, especially in prenatal diagnostics. However, in most cases it is impossible to define them precisely because the final clinical presentation is a result of an overlap, usually due to different sizes of deletions and/or duplications not only chromosome 3 but also of translocation partner chromosome. In this article, we present a prenatal diagnosis of the 3q duplication syndrome in a foetus, arising from a balanced insertion ins (7,3)(q21.2;q12.3q29) carried by the mother.Case presentationThe article presents a case of a 29-year-old woman referred to the Genetic Outpatient Clinic for consultation in the 12th week of her fifth pregnancy with a diagnosis of generalised hydrops foetalis. The analysis of karyotype using GTG technique and FISH allowed diagnosis of a balanced aberration in the mother, and determined the type of chromosomal rearrangement, which allowed the identification of the origin of the additional genetic material in the foetus and the previous malformed child of the same couple. The use of molecular karyotyping techniques (FISH and aCGH) allowed a precise determination of the size of the imbalanced fragments in the affected siblings.ConclusionsThe aCGH technique is particularly valuable for the diagnostics of submicroscopic deletions and duplications, if no imbalanced chromosomal aberrations are detected by routine cytogenetic tests. It is also a valuable technique for identifying and fully characterizing genetic material of unknown origin, which can’t be identified using routine cytogenetic techniqes. However, it does not allow identification of balanced aberrations in carriers.

Monosomy chromosome 21 compensated by 21q22.11q22.3 duplication in a case with small size and minor anomalies

BackgroundPartial monosomy 21 is a rare finding with variable sizes and deletion breakpoints, presenting with a broad spectrum of phenotypes.Case presentationWe report a 10-month-old boy with short stature, minor anomalies and mild motor delay. The patient had a monosomy 21 and duplication of the 21q22.11q22.3 region on the remaining derivative chromosome 21 which represents a partial 21q uniparental disomy of paternal origin, upd(21q22.11q22.3)pat. The abnormalities were characterized by karyotyping, FISH, chromosomal microarray, and genotyping.ConclusionsThis is the first case showing a monosomy 21 compensated by upd(21q22.11q22.3) as a mechanism of genomic rescue. Because there is no strong evidence showing imprinting on chromosome 21, the uniparental disomy itself is not associated with abnormal phenotype but has reduced phenotype severity of monosomy 21. We reviewed the previously published cases with isolated 21q deletions and identified a common deletion of 5.7 Mb associated with low birth weight, length and head circumference in the 21q21.2 region.

'Blastoid' variant of Burkitt lymphoma with additional partial 1q tetrasomy.

Burkitt lymphoma is cytogenetically characterized by t(8;14)(q24;q32) translocation, sometimes accompanied by additional cytogenetic abnormalities. These abnormalities usually result in more aggressive clinical presentation and morphology of the disease. The current report presens a case of Burkitt lymphoma with t(8;14)(q24;q32) accompanied by partial tetrasomy of chromosome 1(47,XY,+1,i(1)(q10),t(8;14)(q24;q32)[2]/46,XY[18]). The patient was a 59-year-old male who presented with abdominal pain, leukocytosis and tumor lysis syndrome. No lymphadenopathy was noted. Cerebrospinal fluid analysis revealed atypical lymphocytes. A peripheral blood smear revealed tumor cells exhibiting distinct ‘blastoid’ morphology: Prominent nucleoli, basophilic cytoplasm, occasional cytoplasmic vacuoles. Flow cytometry demonstrated B cells expressing cluster of differentiation (CD)10 and cytoplasmic kappa light chain restriction without surface expression of immunoglobulins and CD20. A bone marrow biopsy revealed hematopoiesis, with a 90% replacement with atypical lymphocytes. The patient was treated with chemotherapy. Following the first cycle of treatment, the patient developed neutropenic fever, bacteremia and died a few days later. Gain of chromosome 1q in addition to characteristic for Burkitt lymphoma t(8;14)(q24;q32) resulted in immature ‘blastoid’ morphology and the immunophenotype of tumor cells, leukemic presentation without lymph node involvement and a highly aggressive clinical course.

SNP array analysis of three cases with partial 21q trisomy

To analyze three cases with partial 21q trisomy, and correlate their genotypes with phenotypes. G-banding chromosomal analysis and single nucleotide polymorphism (SNP array) were performed for the three cases and their parents. SNP array has detected partial 21q trisomy in three cases and one mother, with variable size and location of the duplications. Case 1 harbored a 12.35 Mb duplication at 21q22.11q22.3, which spanned the Down syndrome critical region. Case 2 harbored a 35.32 Mb duplication at 9p24.3p13.3 and a 14.42 Mb duplication at 21q11.2q21.3, with the former spanning the partial 9p trisomy syndrome critical region excluding the Down syndrome critical region, and was inherited from his mother. Case 3 harbored a 4.17 Mb tetraploidy at 21q11.2q21.1 in the form of mosaicism, which spared the Down syndrome critical region. His mother carried a 4.17 Mb triploidy at 21q11.2q21.1, which was also a mosaicism. Partial 21q trisomy may occur in various forms and its clinical phenotypes are heterogeneous. Combined use of genetic techniques, particularly SNP array, is crucial for diagnosing partial 21q trisomy and delineating its genotype-phenotype correlation.

A rare occurrence of two large de novo duplications on 1q42-q44 and 9q21.12-q21.33

De novo partial distal 1q trisomy is uncommon and mostly occurs in combination with monosomy of another chromosome due to a parental translocation. Distal 1q trisomy co-occurring with another de novo duplication on a separate chromosome is extremely rare. Here, we reported a patient carrying two large de novo interstitial duplications including a 20Mb duplication at 1q42-q44 and a 14.2Mb duplication at 9q21.12-q21.33. The patient presented with features of pre- and postnatal growth retardation, low birth weight, failure to thrive, developmental delay and frequent infection. Her dysmorphic features included macrocephaly, prominent forehead, triangular face, wide fontanelle, hypertelorism, flat nasal bridge, tented mouth, micrognathia, protruding and low-set ears, slender limbs with toe-walking appearance. In addition, she presented with subdural hematoma. The clinical presentations of this patient are mostly consistent with those of distal 1q trisomy syndrome or 9q interstitial duplication. The interstitial 1q trisomy may have contributed to the macrocephaly, prominent forehead and limb abnormalities of our patient. Either or both de novo duplications could have contributed to the features of growth retardation, developmental delay and dysmorphic features including hypertelorism, low-set ears and abnormal nose/nasal bridge.

Recurrent fetal syndromic spina bifida associated with 3q26.1-qter duplication and 5p13.33-pter deletion due to familial balanced rearrangement

ObjectiveNeural tube defects belong to the second most common group of congenital anomalies, after heart defects, which can be diagnosed by prenatal ultrasonography. Rarely, neural tube defects can be associated with chromosomal abnormalities, including full and partial aneuploidies. We report a familial fetal case with syndromic spina bifida and discuss its association with partial 3q duplication and partial 5p deletion. Materials and methodsClinical findings of three affected family members in two generations and two carriers of the balanced translocation are described. Conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis of the carrier, as well as subtelomeric multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analysis on the DNA extracted from affected family members was performed. ResultsSubtelomeric FISH analysis of the proposita revealed balanced reciprocal translocation between the long arm of chromosome 3 and short arm of chromosome 5. Subtelomeric MLPA screening of the first child revealed the deletion in 5p15.33 and duplication in 3q29 chromosomal loci, the finding consisting of the unbalanced rearrangement involving the short arm of chromosome 5 and long arm of chromosome 3. Array CGH analysis of the DNA of the second affected child revealed a 31.1Mb duplication of 3q26.1-qter and a 33.6Mb deletion of 5p13.33-pter. ConclusionOur report serves to emphasize the consistency in the prenatal sonographic feature of spina bifida in consecutive pregnancies with fetuses associated with partial trisomy 3q (3q26.1-qter) and partial monosomy 5p (5p13.33-pter). The use of molecular cytogenetic technologies such as array CGH and FISH is important for clarifying any type of unbalanced chromosome rearrangement.

Cytogenetic and molecular characterization of a patient with partial 6q trisomy and 1q monosomy

To analyze a girl with moderate mental retardation and speech and language disorders with cytogenetics technique and next-generation sequencing (NGS). G-banding chromosome analysis was used to ascertain the karyotype of the child and her parents, and NGS was used for determining the size and origin of the abnormal chromosome fragment. Mate-pair and PCR were used to determine its parental origin. The karyotype of the child was determined to be 46,XX,add(1)(q44)dn, while her parents were both normal. NGS revealed that the child has harbored a partial trisomy of 6q24.3-q27, and the breakpoint was mapped to at 6q24.3q27. In addition, a 2.5 Mb microdeletion at 1q44 was found in the patient. No recognizable phenotype was associated with 1q44 deletion. The abnormal phenotypes presented by the child may be attributed to the 6q24.3-q27 triplication. Compared with conventional cytogenetic analysis, NGS has a much higher resolution and great accuracy.

Dissection of partial 21q monosomy in different phenotypes: clinical and molecular characterization of five cases and review of the literature.

BackgroundPartial deletion of chromosome 21q is a very rare chromosomal abnormality associated with highly variable phenotypes, such as facial dysmorphic features, heart defects, seizures, psychomotor delay, and severe to mild intellectual disability, depending on the location and size of deletions. So far, three broad deletion regions of 21q have been correlated with the clinical phenotype.ResultsWe described the clinical and genetic features of three family members (father and two siblings) and other two unrelated patients with very wide range in age of diagnosis. All of them showed intellectual disability with very variable symptoms, from mild to severe, and carried 21q interstitial deletions with different sizes and position, as detected by conventional karyotype and array-CGH.ConclusionsOur study provided additional cases of partial 21q deletions, allowing to better delineate the genotype-phenotype correlations. In contrast to previous observations, we showed that deletions of the 21q proximal region are not necessarily associated with severe phenotypes and, therefore, that mild phenotypes are not exclusively related to distal deletions. To the best of our knowledge, this is the first report showing 21q deletions in adult patients associated with mild phenotypes, mainly consisting of neurobehavioral abnormalities, such as obsessive-compulsive disorders, poor social interactions and vulnerability to psychosis.

Detailed analysis of 26 cases of 1q partial duplication/triplication syndrome.

Partial 1q trisomy syndrome is a rare disorder. Because unbalanced chromosomal translocations often occur with 1q trisomy, it is difficult to determine whether patient symptoms are related to 1q trisomy or other chromosomal abnormalities. The present study evaluated genotype-phenotype correlations of 26 cases diagnosed with 1q partial trisomy syndrome. DNA microarray was used to investigate the duplication/triplication region of 16 cases. Although there was no overlapping region common to all 26 cases, the 1q41-qter region was frequently involved. One case diagnosed as a pure interstitial trisomy of chromosome 1q by G-banded karyotype analysis was instead found to be a pure partial tetrasomy by CytoScan HD Array. In four 1q trisomy syndrome cases involving translocation, the translocated partner chromosome could not be detected by DNA microarray analyzes despite G-banded karyotype analysis, because there were a limited number of probes available for the partner region. DNA microarray and G-banded karyotyping techniques were therefore shown to be compensatory diagnostic tools that should be used by clinicians who suspect chromosomal abnormalities. It is important to continue recruiting affected patients and observe and monitor their symptoms to reveal genotype-phenotype correlations and to fully understand their prognosis and identify causal regions of symptoms.

Новые горизонты цитогенетики при первичном миелофиброзе

ABSTRACT Aim. To evaluate the potential of a new cytogenetic technique in patients with primary myelofibrosis (PMF). Materials and methods. 48-hour blood cell cultures (accord-ing to Singh et al., 2013) were used for cytogenetic study in 11 PMF patients (5 female, 6 men, aged 32–60 years; median 48.6 years). GTG-banding and different types of fluorescence in situ hybridization (FISH) techniques were used for identifica-tion of chromosomal aberrations. Results. The incidence of abnormal karyotypes in blood cul-tures was significantly higher than that in standard bone mar-row cultures (82 vs 27 %; p < 0.01). The polyploid clones were found in blood cultures of 45 % of patients. Structural chro-mosomal aberrations were found in chromosomes 6, 1, 3, as well as 16 and 17 (in 2 and 1 patients with each aberration, respectively). In all but one patients these abnormalities in dip-loid and polyploid metaphases were identical. Partial 1q tri-somy resulted from adding of additional (1q21–1q44) material translocated to the short arm of chromosome 5 to the material of 2 normal homologue of chromosome 1. It seems that 1q+, i(17q) and some others chromosomal abnormalities were sec-ondary, whereas 6p21 locus involvement may be a primary defect in PMF. The t(3;6)(q25;p21) translocation described for the first time and confirmed by FISH should be considered a variant of well-known translocation t(1;6). Allo-HSCT in 2 pa-tients with 1q+ was successful, whereas there were problems with engraftment in a female patient with prognostically unfa-vorable t(3;3)(q21;q26) translocation associated with the

Inherited Unbalanced Chromosome from Parent with Balanced Translocation: A Case Report and Review of Literature

Reciprocal translocations are common, and the translocation heterozygote (carrier) may have a risk to have a child who would be mentally and physically abnormal due to a segmental aneusomy. The carriers of balanced translocation mostly do not have recognizable phenotypic expression, however, they can produce unbalanced chromosome, which is transmitted to next generation through fertilization of gametes carrying the derivative chromosome. We describe a 4-year-old boy with partial 10q trisomy and distal 13qmonosomy. The patient presented with delayed milestones, dysmorphic face, congenital heart defect, renal and skeletal anomalies. The conventional cytogenetic analysis showed a 46,XY, add(13q) karyotype. The child inherited the unbalanced chromosome from mother who was a carrier of balanced reciprocal translocation,t(10;13)(p24.2;q33.1). The phenotype observed in our patient resulted from the combination of those defects described in the isolated dup(10q) and distal del(13q) syndromes but predominantly resembles the children with distal trisomy 10q syndrome. Our finding are in concordance with the literature and supports the importance of critical regions like 10q24 and 13q32 for the phenotypic expression of distal 10q trisomy syndrome and distal 13q trisomy syndrome respectively.

MG-121 Five new patients with pure distal 1q trisomy, review of the literature and phenotype redefinition

Background Pure distal 1q trisomy is rare and there is limited information on genotype-phenotype correlation. The common 1q trisomy phenotype attributed to the 1q42qter segment is based on a small number of patients and consists of small for gestational age, developmental delay, macrocephaly, dysmorphic features and heart defects. Objective To clarify the genotype-phenotype correlation of pure distal 1q trisomy. Design/method We report five patients with pure distal 1q trisomy: 1q32.2qter (patient 1), 1q41q44 (patient 2), 1q43qter (patient 5) and 1q42.13qter in two siblings (patient 3 and 4). A PubMed search was done to identify patients with trisomies distal to 1q32. Patients with pure 1q trisomies that matched the duplications found in our patients were selected. Results Thirty-three patients have been reported with partial trisomy distal to 1q32. Only 17 patients with pure 1q trisomy matched our patients’: ten for 1q32qter, four for 1q41q44, two for 1q42qter and one for 1q43qter. Our patients presented additional features than the common 1q trisomy phenotype. Patients 1, 2, 3 and 4 have had frequent infections with normal immunological status. Patients 1, 3 and 4 had significant sleeping problems. Patients 3 and 4 have camptodactyly and patient 4 had hypertrophied cardiomyopathy. Patients 4 and 3 respectively have moderate and mild intellectual deficiency, a feature that was thought to be mostly normal distal to the 1q42 region. Conclusions The partial 1q trisomy phenotype is constantly expanding. An improved definition allows for the identification of critical regions and better genetic counselling and follow up.

Prenatal molecular cytogenetic analysis of a mild dysmorphic fetus with a huge unbalance karyotype involving partial 9p deletion and partial 18q duplication

Partial 9p deletion syndrome and partial 18q duplication syndrome each have distinct clinical features. We describe the prenatal molecular cytogenetic analysis of a de novo unbalanced karyotype with deletion of 9p23-pter and duplication of 18q12.2-qter in a mild dysmorphic female fetus. Fetal ultrasonography was performed and detailed karyotype analyses were conducted using a combination of G-banding, SKY analysis and FISH with chromosome arm specific sub-telomeric DNA probes and chromosomal region specific BAC clone probes. The fetal sonography and fetal echocardiography at 17 weeks’ gestation did not reveal any anomaly while the fetus had a large unbalance karyotype of 46,XX,der(9)t(9;18) (p23;q12.2) de novo. Its external phenotype at 21 weeks appeared to have some mild dysmorphic features including hypertelorism, low-set ears, micrognathia/retrognathia, clenched hands and rocker bottom feet. These dysmorphic features are seen in the Edward syndrome but with milder degrees.

Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma.

The International Neuroblastoma Pathology Classification (INPC) has a prognostic impact that distinguishes two categories of neuroblastoma: favorable histology (FH) and unfavorable histology (UH). We analyzed 92 cases of neuroblastoma with the INPC evaluation and genomic grouping to investigate the correlation between the INPC and genomic signature, together with their prognostic significance. The correlation of UH tumor and partial gains and/or losses (GGP), as well as the correlation of FH tumor and whole gains and/or losses (GGW), was statistically significant. Both UH and GGP were late-onset (median age at diagnosis was 36 and 48 months, respectively) and had poor prognosis (overall survival rate [OS], 43.1% and 42.4%, respectively). In contrast, both FH and GGW were early-onset (median age at diagnosis, 4 and 9.5 months, respectively) and had favorable prognosis (OS, 88.6% and 87.1%, respectively). Unfavorable histology and GGP had significantly inferior OS compared to FH and GGW. Overall survival was not significantly different among the genomic groups in FH; however, it was inferior in UH with GGP. In UH with a single copy MYCN, genomic subgroups GGP2s (both 1p and 11q losses) and GGP3s (partial 11q loss but not 1p loss) indicated significantly poor prognosis compared to GGP4s (no partial 1p and 11q loss). As INPC and MYCN amplification were found to be the most powerful prognostic biological factors, they should be included with genomic grouping as treatment stratification for patients with UH and single copy of MYCN.