Identification of a rare copy number polymorphic gain at 3q12.2 with candidate genes for familial endometriosis.

Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaß pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaß pathway in predisposition to endometriosis.

[Prenatal diagnosis of a fetus with 1p36 deletion syndrome and 3p26.3p25.2 duplication].

OBJECTIVE: To explore the characteristics of a fetus with chromosome 1p36 deletion syndrome and 3p26.3p25.2 duplication. METHODS: A pregnant woman who had attended the Genetic Counseling Clinic of Linyi People's Hospital on February 22, 2022 and her fetus were selected as the study subjects. Clinical data were collected. Chromosomal karyotyping, fluorescence in situ hybridization (FISH) and chromosomal microarray analysis (CMA) were carried out for the prenatal diagnosis. RESULTS: Ultrasonography at 24th gestational week revealed that the fetus had ventricular septal defect, single umbilical artery, and slight widening of left lateral ventricle (12 mm). The woman was found to have a karyotype of 46,XX,t(1;3)(p36.22;p25.2), and the result of FISH was t(1;3)(3pter+,1qter+;1pter+,3qter+). The fetus was found to have a karyotype of 46,X?,add(1)(p36), and CMA confirmed that it has a 9.0 Mb deletion at 1p36.33p36.22 and a 12.6 Mb duplication at 3p26.3p25.2. Combining the maternal karyotype, the molecular karyotype of the fetus was determined as 46,X?,der(1)t(1;3)(p36.22;p25.2)mat.arr[hg19]1p36.33p36.22(849467_9882666)×1, 3p26.3p25.2(61892_12699607)×3, with the former known to be associated with 1p36 deletion syndrome. CONCLUSION: The fetus was diagnosed with 1p36 deletion syndrome, and its 1p36.33p36.22 deletion and 3p26.3p25.2 duplication had both derived from the balanced translocation carried by its mother.

Quercetin Impairs the Growth of Uveal Melanoma Cells by Interfering with Glucose Uptake and Metabolism.

Monosomy 3 in uveal melanoma (UM) increases the risk of lethal metastases, mainly in the liver, which serves as the major site for the storage of excessive glucose and the metabolization of the dietary flavonoid quercetin. Although primary UMs with monosomy 3 exhibit a higher potential for basal glucose uptake, it remains unknown as to whether glycolytic capacity is altered in such tumors. Herein, we initially analyzed the expression of n = 151 genes involved in glycolysis and its interconnected branch, the "pentose phosphate pathway (PPP)", in the UM cohort of The Cancer Genome Atlas Study and validated the differentially expressed genes in two independent cohorts. We also evaluated the effects of quercetin on the growth, survival, and glucose metabolism of the UM cell line 92.1. The rate-limiting glycolytic enzyme PFKP was overexpressed whereas the ZBTB20 gene (locus: 3q13.31) was downregulated in the patients with metastases in all cohorts. Quercetin was able to impair proliferation, viability, glucose uptake, glycolysis, ATP synthesis, and PPP rate-limiting enzyme activity while increasing oxidative stress. UMs with monosomy 3 display a stronger potential to utilize glucose for the generation of energy and biomass. Quercetin can prevent the growth of UM cells by interfering with glucose metabolism.

Variants in 3p24.3 predicts the risk of early neurological deterioration in large artery atherosclerotic stroke.

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.

[Application of optical genome mapping technology for the detection of chromosomal structural variations].

OBJECTIVE: To assess the value of optical genome mapping (OGM) for the detection of chromosomal structural abnormalities including ring chromosomes, balanced translocations, and insertional translocations. METHODS: Clinical data of four patients who underwent pre-implantation genetic testing concurrently with OGM and chromosomal microarray analysis at the Center of Reproductive Medicine of the Sixth Affiliated Hospital of Sun Yat-sen University from January to October 2022 due to chromosomal structural abnormalities were selected as the study subjects. Some of the results were verified by multi-color fluorescence in situ hybridization. RESULTS: The OGM has successfully detected a balanced translocation and fine mapped the breakpoints in a patient. Among two patients with insertional translocations, OGM has provided more refined breakpoint locations than karyotyping analysis in a patient who had chromosome 3 inserted into chromosome 6 and determined the direction of the inserted fragment. However, OGM has failed to detect the chromosomal abnormality in a patient with chromosome 8 inserted into the Y chromosome. It has also failed to detect circular signals in a patient with ring chromosome mosaicism. CONCLUSION: OGM has successfully detected chromosomal structural variations in the four patients and provided assistance for their diagnosis.

[The role of SF3B1 mutations in EVI1-rearranged myeloid neoplasms].

In acute myeloid leukemia (AML), EVI1 rearrangement represented by inv(3)(q21q26) or t(3;3)(q21;q26) causes EVI1 overexpression via structural rearrangement of an enhancer, and confers poor prognosis. My colleagues and I performed a mutational analysis of EVI1-rearranged myeloid neoplasms and identified SF3B1, a core RNA splicing factor, as the most commonly co-mutated gene. Indeed, latent leukemia development in transgenic mice bearing the humanized inv(3)(q21q26) allele was significantly accelerated by co-occurrence of Sf3b1 mutation. Intriguingly, we found that this SF3B1 mutant induced mis-splicing of EVI1 itself, which generated an aberrant EVI1 isoform with in-frame insertion of 6 amino acids near the DNA-binding domain of EVI1. This aberrant EVI1 isoform exhibited DNA-binding activity different from wild-type EVI1 and significantly enhanced the self-renewal capacity of murine hematopoietic stem cells. We also identified the cryptic branch point and exonic splicing enhancer required for this EVI1 mis-splicing induced by the SF3B1 mutant. These data provide a basis for further elucidation of the molecular mechanism and potential therapeutic candidates for EVI1-rearranged AML.

PRUNE1 (located on chromosome 1q21.3) promotes multiple myeloma with 1q21 Gain by enhancing the links between purine and mitochondrion.

Patients with multiple myeloma (MM) with chromosome 1q21 Gain (1q21+) are clinically and biologically heterogeneous. 1q21+ in the real world actually reflects the prognosis for gain/amplification of the CKS1B gene. In this study, we found that the copy number of prune exopolyphosphatase 1 (PRUNE1), located on chromosome 1q21.3, could further stratify the prognosis of MM patients with 1q21+. Using selected reaction monitoring/multiple reaction monitoring (SRM/MRM) analysis, liquid chromatography-tandem mass spectrometry (LC-MS/MS), transmission electron microscopy (TEM), confocal fluorescence microscopy, calculation of adenosine triphosphate (ATP), intracellular reactive oxygen species (ROS) and mitochondrial oxygen consumption rates (OCRs), we demonstrated for the first time that PRUNE1 promotes the proliferation and invasion of MM cells by stimulating purine metabolism, purine synthesis enzymes and mitochondrial functions, enhancing links between purinosomes and mitochondria. SOX11 was identified as a transcription factor for PRUNE1. Through integrated analysis of the transcriptome and proteome, CD73 was determined to be the downstream target of PRUNE1. Furthermore, it has been determined that dipyridamole can effectively suppress the proliferation of MM cells with high-expression levels of PRUNE1 in vitro and in vivo. These findings provide insights into disease-causing mechanisms and new therapeutic targets for MM patients with 1q21+.

[Genetic diagnosis of Branchio-Oto syndrome pedigree due to a de novo heterozygous deletion of EYA1 gene].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with Branchio-Oto syndrome (BOS). METHODS: A pedigree with BOS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples of the proband and her parents were collected. Whole exome sequencing (WES) was carried out for the proband. Multiplex ligation-dependent probe amplification (MLPA) was used to verify the result of WES, short tandem repeat (STR) analysis was used to verify the relationship between the proband and her parents, and the pathogenicity of the candidate variant was analyzed. RESULTS: The proband, a 6-year-old girl, had manifested severe congenital deafness, along with inner ear malformation and bilateral branchial fistulae. WES revealed that she has harbored a heterozygous deletion of 2 466 kb at chromosome 8q13.3, which encompassed the EYA1 gene. MLPA confirmed that all of the 18 exons of the EYA1 gene were lost, and neither of her parents has carried the same deletion variant. STR analysis supported that both of her parents are biological parents. Based on the guidelines from the American College of Medical Genetics and Genomics, the deletion was classified as pathogenic (PVS1+PS2+PM2_Supporting+PP4). CONCLUSION: The heterozygous deletion of EYA1 gene probably underlay the pathogenicity of BOS in the proband, which has provided a basis for the clinical diagnosis.

Evidence of cancer-linked rodent zoonoses from biophysical genomic variations.

As a mechanism to explore the role of environmental adaptation in establishing the optimal distribution of single nucleotide polymophisms (SNPs) within resident homeostatic populations, relationships between quantified environmental parameters and the frequencies of the variants are being explored. We have performed sequential double-blind scans on more than 30% of chromosome 3 in an attempt to discover possible relationships using simple mathematical functions that are indicative of "adaptive forces" on the variants due to specific quantified environmental agents. We have found an association of rs13071758 with rodent zoonotic diseases. This variant is within the FHIT gene, which spans the most fragile of the common fragile sites in human lymphoblasts. FHIT, which is highly sensitive to environmental carcinogens, is partially lost in most human cancers. This finding is consistent with other studies postulating an association between rodent zoonoses and cancer. We quantify the adaptive force on the T allele as 0.28 GEUs per unit of zoonotic rodent host richness.

Delineation of molecular characteristics of congenital myasthenic syndromes in Indian families and review of literature.

Congenital myasthenic syndromes (CMS) are rare, heterogeneous, and often treatable genetic disorders depending on the underlying molecular defect. We performed a detailed clinical evaluation of seven patients from five unrelated families. Exome sequencing was performed on five index patients. Clinically significant variants were identified in four CMS disease-causing genes: COLQ (3/7), CHRNE (2/7), DOK7 (1/7), and RAPSN (1/7). We identified two novel variants, c.930_933delCATG in DOK7 and c.1016_1032 + 2dup in CHRNE . A common pathogenic variant, c.955-2A>C, has been identified in COLQ -related CMS patients. Homozygosity mapping of this COLQ variant in patients from two unrelated families revealed that it was located in a common homozygous region of 3.2 Mb on chromosome 3 and was likely to be inherited from a common ancestor. Patients with COLQ variants had generalized muscle weakness, those with DOK7 and RAPSN variants had limb-girdle weakness, and those with CHRNE variants had predominant ocular weakness. Patients with COLQ and DOK7 variants showed improvement with salbutamol and CHRNE with pyridostigmine therapy. This study expands the mutational spectrum and adds a small but significant cohort of CMS patients from India. We also reviewed the literature to identify genetic subtypes of CMS in India.

Efficient site-specific integration in CHO-K1 cells using CRISPR/Cas9-modified donors.

BACKGROUND: Conventional methods applied to develop recombinant CHO (rCHO) cell line as a predominant host for mammalian protein expression are limited to random integration approaches, which can prolong the process of getting the desired clones for months. CRISPR/Cas9 could be an alternative by mediating site-specific integration into transcriptionally active hot spots, promoting homogenous clones, and shortening the clonal selection process. However, applying this approach for the rCHO cell line development depends on an acceptable integration rate and robust sites for the sustained expression. METHODS AND RESULTS: In this study, we aimed at improving the rate of GFP reporter integration to the Chromosome 3 (Chr3) pseudo-attP site of the CHO-K1 genome via two strategies; these include the PCR-based donor linearization and increasing local concentration of donor in the vicinity of DSB site by applying the monomeric streptavidin (mSA)-biotin tethering approach. According to the results, compared to the conventional CRISPR-mediated targeting, donor linearization and tethering methods exhibited 1.6- and 2.4-fold improvement in knock-in efficiency; among on-target clones, 84% and 73% were determined to be single copy by the quantitative PCR, respectively. Finally, to evaluate the expression level of the targeted integration, the expression cassette of hrsACE2 as a secretory protein was targeted to the Chr3 pseudo-attP site by applying the established tethering method. The generated cell pool reached 2-fold productivity, as compared to the random integration cell line. CONCLUSION: Our study suggested reliable strategies for enhancing the CRISPR-mediated integration, introducing Chr3 pseudo-attP site as a potential candidate for the sustained transgene expression, which might be applied to promote the rCHO cell line development.

Triplications of chromosome 1p36.3, including the genes GABRD and SKI, are associated with a developmental disorder and a facial gestalt.

Triplication of chromosomal region 1p36.3 is a rare genomic rearrangement. In this report, we delineate the phenotypic spectrum associated with 1p36.3 triplications. We describe four patients with microtriplications of variable size, but with a strong phenotypic overlap, and compare them to previously described patients with an isolated triplication or duplication of this region. The 1p36.3 triplication syndrome is associated with a distinct phenotype, characterized by global developmental delay, moderate intellectual disability, seizures, behavioral problems, and specific facial dysmorphic features, including ptosis, hypertelorism, and arched eyebrows. The de novo occurrence of these microtriplications demonstrates the reduced reproductive fitness associated with this genotype, in contrast to 1p36.3 duplications which are mostly inherited and can be associated with similar facial features but with a less severe developmental phenotype. The shared triplicated region encompasses four disease-related genes of which GABRD and SKI are most likely to contribute to the phenotype.

Whole-genome analysis of recombinant inbred rice lines reveals a quantitative trait locus on chromosome 3 with genotype-by-environment interaction effects.

Elucidating genotype-by-environment interactions is fundamental for understanding the interplay between genetic and environmental factors that shape complex traits in crops. Genotype-by-environment interactions are of practical importance, as they determine the performance of cultivars grown in different environments, prompting the need for an efficient approach for evaluating genotype-by-environment interactions. Here, we describe a method for genotype-by-environment detection that involves comparing linear mixed models. This method successfully detected genotype-by-environment interactions in rice (Oryza sativa) recombinant inbred lines grown at 3 locations. We identified a quantitative trait locus (QTL) on chromosome 3 that was associated with heading date, grain number, and leaf length. The effect of this QTL on plant growth-related traits varied with environmental conditions, indicating the presence of genotype-by-environment interactions. Therefore, our method enables a powerful genotype-by-environment detection pipeline that should facilitate the production of high-yielding crops in a given environment.

Screening and characterization of sex-specific sequences through 2b-RAD sequencing in American shad (Alosa sapidissima).

American shad (Alosa sapidissima), introduced from the United States, has become one of the most expensive farmed fish in the aquatic product market of China. The shad reveals significant sexual dimorphism in growth and behaviors. For the study, five male-specific tags were identified in two-generation breeding populations of Alosa sapidissima and were verified by PCR amplification. Averages of 10,245,091 and 8,685,704 raw and enzyme reads were obtained by high-throughput sequencing of the 2b-RAD library, respectively. 301,022 unique tags were obtained from the sequences of twenty samples with sequencing depths of 0 to 500. Finally, 274,324 special tags and 29,327 SNPs were selected with a sequencing depth of 3 to 500. Eleven preliminary screening male-specific tags and three male heterogametic SNP loci were isolated. After verification by PCR amplification, five male-specific sequences of 27 bp located on chromosome 3 were screened out. Chromosome 3 could be assumed to be the sex chromosome of Alosa sapidissima. Sex-specific markers will provide invaluable and systematic animal germplasm resources to allow for the precise identification of neo-males for the all-female breeding of Alosa sapidissima in commercial aquaculture.

Genetic Status Affects Disease-Specific Mortality But Not the Incidence of Local Recurrence in Patients with Uveal Melanoma.

PURPOSE: Increased disease-specific mortality has been observed among patients with local recurrence (LR) from uveal melanoma (UM), but the underlying mechanism is unknown. The purpose of this study was to determine if copy number alterations of chromosomes 3 and/or 8q, at the time of diagnosis, increase the incidence of LR and if disease-specific mortality among patients with LR depends on the chromosome status of the primary tumor. DESIGN: Retrospective cohort study. PARTICIPANTS: The study included 239 consecutive patients with primary UM (choroidal or ciliary body) treated with Ruthenium-106 (Ru-106) brachytherapy from January 2009 to December 2019 at a single national referral center. METHODS: Cox regression modeling and Kaplan-Meier analyses were used to assess the effect of the status of chromosomes 3 and 8q on the incidence of LR and disease-specific mortality after the event of LR. Multistate models were used to illustrate the probabilities over time of patients being alive and disease-free, alive with LR, dead from UM metastases, or dead from other causes split on the status of chromosomes 3 and 8q. MAIN OUTCOME MEASURES: Incidence of LR and disease-specific mortality. RESULTS: Local recurrence was observed in 42 patients (16%). Overall incidence of LR was not affected by aberrations of chromosomes 3 and/or 8q (P = 0.87). Although LR occurred earlier in patients with aberrations of chromosomes 3 and/or 8q compared with patients with a normal copy number of chromosomes 3 and 8q, the median time from primary diagnosis to LR was 1.6 years (interquartile range [IQR], 1.0-2.0) and 3.2 years (IQR, 2.1-5.0), respectively. Cox regression found LR to be an independent risk factor for disease-specific mortality (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-5.0) among all patients, but multistate models demonstrated a low risk of disease-specific death among patients with normal chromosomes 3 and 8q status, even after an LR. CONCLUSIONS: Copy number alterations of chromosome 3 and/or 8q in the primary UM did not increase the overall incidence of LR. However, the development of an LR enhanced the risk of disease-specific mortality among patients with copy number alterations of chromosomes 3 and/or 8q. Even after an LR, disease-specific mortality remained low among patients with normal copy numbers of chromosomes 3 and 8q. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

BACKGROUND: Duplications 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 PRESENTATION: Hereby, 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. CONCLUSIONS: Advanced 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.

Gene-by-gene screen of the unknown proteins encoded on Plasmodium falciparum chromosome 3.

Taxon-specific proteins are key determinants defining the biology of all organisms and represent prime drug targets in pathogens. However, lacking comparability with proteins in other lineages makes them particularly difficult to study. In malaria parasites, this is exacerbated by technical limitations. Here, we analyzed the cellular location, essentiality, function, and, in selected cases, interactome of all unknown non-secretory proteins encoded on an entire P. falciparum chromosome. The nucleus was the most common localization, indicating that it is a hotspot of parasite-specific biology. More in-depth functional studies with four proteins revealed essential roles in DNA replication and mitosis. The mitosis proteins defined a possible orphan complex and a highly diverged complex needed for spindle-kinetochore connection. Structure-function comparisons indicated that the taxon-specific proteins evolved by different mechanisms. This work demonstrates the feasibility of gene-by-gene screens to elucidate the biology of malaria parasites and reveal critical parasite-specific processes of interest as drug targets.

Cytogenetic Abnormalities for Predicting the Risk of Metastases in Choroidal and Ciliary Body Melanoma.

Purpose: Choroidal melanoma (CM) and ciliary body melanoma (CBM) are the two most common subtypes of uveal melanoma. Starting from the observation that CBM tends to have a higher metastatic potential than CM, we hypothesized that specific cytogenetic abnormalities could be associated with tumor location - reflecting distinct genetic signatures that would drive the risk of distant spread. Methods: Chromosomal alterations were investigated by molecular cytogenetic techniques in 217 and 97 patients with CM and CBM, respectively. Cox proportional hazards regression analysis was used to identify the independent predictors of distant metastasis. Results: Patients with CBM had larger tumor sizes (P < 0.001), higher disease stages (P < 0.001), and more frequently showed distant metastasis (P = 0.002) than those with CM. On analyzing the entire study cohort, we found that specific chromosomal alterations - including chromosome 8p loss (P < 0.001), 1p loss (P < 0.001), and monosomy 3 (P < 0.005) - were independent predictors of distant metastasis. Based on a decision-tree learning algorithm, we identified three specific subgroups of patients with uveal melanoma at high risk of distant spread. Monosomy 3 occurred significantly more frequently in patients with T3 CBM tumors. Conclusions: Specific cytogenetic abnormalities - including chromosome 8p loss, 1p loss, and monosomy 3 - are independent risk factors for distant metastasis in uveal melanoma. Larger tumor size at presentation and monosomy 3 contribute to a higher metastatic risk in patients with CBM.

Coexistence of 3q29 microdeletion syndrome and Takayasu arteritis: A case report.

Takayasu arteritis (TAK) is a rare type of large and medial vessel systemic vasculitis. A variety of factors are thought to play a role in the occurrence and development of TAK such as human leukocyte antigen-B52, autoimmunity, inflammation and environmental factors. 3q29 microdeletion syndrome is also a very rare inherited disease, which includes intellectual disability, growth retardation and neuropsychiatric disorders. Here, we present a case with concomitant TAK and 3q29 microdeletion syndrome. A 22-year-old woman presented to the emergency department with sudden bilateral vision loss and severe headache. During physical examination, the patient was noted to have a difference in blood pressure between extremities. Computed tomography angiography revealed vascular wall inflammation in the abdominal aorta. Based on clinical and radiographical findings, a diagnosis of TAK was made. Concurrently, the patient was found to have short stature and intellectual disability. A possible genetic etiology was sought out. Chromosome analysis showed a 1.5 Mb heterozygous deletion on chromosome 3 and a diagnosis of 3q29 microdeletion was made. Additional imaging also revealed a split cord in medulla spinalis along with hemivertebrae and fusion anomalies, neither of which were reported in TAK or 3q29 microdeletion cases in the literature.