Dysregulation of KRT19, TIMP1, and CLDN1 gene expression is associated with thyroid cancer.

Thyroid nodules are the main indicators of thyroid cancer, their malignancy is evaluated by cytological analysis and imaging technology, however, there are still cases where the result is not enough to classify thyroid cancer. Therefore, there is a necessity for accurate molecular biomarkers to collaborate in the diagnosis. Here, we analyzed the mRNA relative expression of CLDN1, TIMP1, and KRT19 genes in FNA of malignant (n = 48) and benign (n = 49) thyroid nodules by RT-qPCR analysis to assess their predictive value as cancer biomarkers. We identified a significant overexpression of the three transcripts in malignant nodules, therefore, the evaluation of their predictive capacity to distinguish between benign and malignant nodule as individual biomarkers were evaluated by logistic regression tests, obtaining promising prediction results to rule out cancer; later by random forest to create a stronger model, we included expression results with clinicopathological characteristics, the best model consists of the three-mRNA level expression with patient's history of cancer (AUC = 0.821, accuracy = 85.4% and sensitivity of 81.1%). These results demonstrate a dysregulated expression of CLDN1, KRT19 and TIMP1 in thyroid cancer, thus, represent a promising panel of biomarkers to be evaluated in indeterminate thyroid nodules.

Placental Microarray Profiling Reveals Common mRNA and lncRNA Expression Patterns in Preeclampsia and Intrauterine Growth Restriction.

Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are major contributors to perinatal morbidity and mortality. These pregnancy disorders are associated with placental dysfunction and share similar pathophysiological features. The aim of this study was to compare the placental gene expression profiles including mRNA and lncRNAs from pregnant women from four study groups: PE, IUGR, PE-IUGR, and normal pregnancy (NP). Gene expression microarray analysis was performed on placental tissue obtained at delivery and results were validated using RTq-PCR. Differential gene expression analysis revealed that the largest transcript variation was observed in the IUGR samples compared to NP (n = 461; 314 mRNAs: 252 up-regulated and 62 down-regulated; 133 lncRNAs: 36 up-regulated and 98 down-regulated). We also detected a group of differentially expressed transcripts shared between the PE and IUGR samples compared to NP (n = 39), including 9 lncRNAs with a high correlation degree (p < 0.05). Functional enrichment of these shared transcripts showed that cytokine signaling pathways, protein modification, and regulation of JAK-STAT cascade are over-represented in both placental ischemic diseases. These findings contribute to the molecular characterization of placental ischemia showing common epigenetic regulation implicated in the pathophysiology of PE and IUGR.

Expression of miR-148b-3p is correlated with overexpression of biomarkers in prostate cancer.

Prostate cancer (PCa) is one of the leading causes of death among men. Genes such as PCA3, PSA, and Fra-1 are suggested to serve as potential tools for the detection of PCa, as they are deregulated during this pathology. A similar event occurs with small non-coding RNAs, called miRNAs, specifically miR-195-5p, miR-133a-3p, and miR-148b-3p, which were analyzed in a Chinese population and suggested to be possible candidates for PCa diagnosis. We evaluated the expression levels of three miRNAs and three genes in tissue samples of PCa and benign prostate disease, such as benign prostatic hyperplasia, or prostatitis, in order to determine their potential as candidates for PCa detection. Our results showed a statistically significant overexpression of 279-fold increase in PSA levels and a 1,012-fold increase in PCA3 levels in PCa patients compared to benign prostate disease patients (p = 0.001 and p = 0.002, respectively). We observed a positive correlation between the expression of miR-148b-3p and the expression of PSA and PCA3 genes, two established biomarkers in PCa. The expression of miR-148b-3p was not related to clinical characteristics, such as age and weight, as observed for the other miRNAs analyzed, suggesting its potential as a biomarker for detection of this pathology.

Familial 3-Way Balanced Translocation Causes 1q43→qter Loss and 10q25.2→qter Gain in a Severely Affected Male Toddler.

Constitutional complex chromosomal rearrangements (CCRs) are rare events that typically involve 2 or more chromosomes with at least 3 breakpoints and can result in normal or abnormal phenotypes depending on whether they disturb the euchromatic neighborhood. Here, we report an unusual balanced CCR involving chromosomes 1, 9, and 10 that causes an unbalanced karyotype in a severely affected toddler. The CCR was initially reported as a maternal 2-way translocation but was reclassified as a 3-way translocation after a microarray analysis of the propositus revealed the involvement of another chromosome not identified by G-banding in his phenotypically normal mother. FISH assays on maternal metaphase cells confirmed that the 1qter region of der(1) was translocated to der(10), whereas the 10qter segment was translocated to der(9), which in turn donated a segment to der(1). Subsequently, this CCR was also identified in her phenotypically normal father (the patient's grandfather). Thus, the patient inherited the previously unreported pathogenic combination of der(1) with a loss of 1q43→qter (including AKT3, ZBTB18, HNRNPU, and SMYD3) and der(9) with a gain of 10q25.2→qter (including FGFR2), leading to a compound phenotype with key features of the 1q43→qter deletion and distal 10q trisomy syndromes. Our observations suggest that the loss of SMYD3 accounts for cardiac defects in a subset of patients. Moreover, due to recurrent miscarriages in this family, our findings allowed improved genetic counseling.

HLA Alleles are Genetic Markers for Susceptibility and Resistance towards Leprosy in a Mexican Mestizo Population.

Despite the use of multidrug therapy, leprosy remains endemic in some countries. The association of several human leucocyte antigen (HLA) alleles and gene polymorphisms with leprosy has been demonstrated in many populations, but the major immune contributors associated to the spectrum of leprosy have not been defined yet. In this study, genotyping of HLA-A, -B, -DR, and -DQ alleles was performed in leprosy patients (n = 113) and control subjects (n = 117) from the region with the highest incidence for the disease in México. The odds of developing leprosy and lepromatous subtype were 2.12- and 2.74-fold higher in carriers of HLA-A*28, and 2.48- and 4.14-fold higher for leprosy and dimorphic subtype in carriers of DQB1*06. Interestingly, DQB1*07 was overrepresented in healthy individuals, compared to patients with leprosy (OR = 0.08) and the lepromatous subtype (OR = 0.06). These results suggest that HLA-A*28 is a marker for predisposition to leprosy and the lepromatous subtype and DQB1*06 to leprosy and the dimorphic subtype, while DQB1*07 might be a resistance marker in this Mestizo population.

Deletion in a regulatory region is associated with underexpression of miR-148b­3p in patients with prostate cancer.

Prostate cancer (PCa) is the leading cause of cancer-related death in men. This pathology is complex and heterogeneous; therefore, elucidating the molecular mechanisms that lead to its origin and progression is imperative. MicroRNAs (miRNAs or miRs) are part of the epigenetic machinery that regulates the expression of human genes, therefore, mutations in the genes that encode them can lead to a dysregulation in their expression, which directly impacts their target genes, which could be oncogenes or tumor suppressor genes. In PCa several dysregulated expression levels of miRNAs are associated with perturbed cellular processes. A differential expression of miRNAs such as miR-145-5p and miR-148-3p has been observed in PCa, possibly due to mutations in regions near the miRNAs. However, the molecular mechanisms that lead to the dysregulation of these miRNAs still need to be clarified. Therefore, the present study aimed to analyze the expression of miRNAs and their relationship with mutations in patients with and without PCa. In total, 71 patients were analyzed: 41 of whom had PCa (CAP group) and 30 with benign pathology (BPD group). Underexpression was observed in miR-145-5p and miR-148b-3p in PCa patients (P=0.03 and P=0.001, respectively). In miR-145-5p, no mutations related to its expression were identified. For miR-148b-3p, a set of mutations were identified in the chr12:54337042/54337043 region, which were grouped into the mutation named DelsAAG. Although this mutation's abnormal allele is related to PCa (P=0.017), a statistically significant difference was observed in the expression of miR-148b-3p between carriers and non-carriers of the mutated allele, identifying a mechanism likely to be involved in the miR-148b-3p dysregulation.

Chromosomal instability in a patient with ring chromosome 14 syndrome: a case report.

BACKGROUND: Ring chromosome 14 syndrome is a rare disorder primarily marked by early-onset epilepsy, microcephaly, distinctive craniofacial features, hypotonia, intellectual disability, and delay in both development and language acquisition. CASE PRESENTATION: A 21-year-old woman with a history of epileptic seizures since the age of 1.5 years presented with distinctive craniofacial features, including a prominent and narrow forehead, sparse and short eyebrows, palpebral ptosis, horizontal palpebral fissures, a broad nasal bridge, a prominent nasal tip, a flat philtrum, hypertelorism, midfacial hypoplasia, horizontal labial fissures, a thin upper lip, crowded teeth, an ogival palate, retrognathia, and a wide neck. Additional physical abnormalities included kyphosis, lumbar scoliosis, pectus carinatum, cubitus valgus, thenar and hypothenar hypoplasia, bilateral hallux valgus, shortening of the Achilles tendon on the left foot, and hypoplasia of the labia minora. Chromosomal analysis identified a ring 14 chromosome with breakpoints in p11 and q32.33. An aCGH study revealed a ~ 1.7 Mb deletion on chromosome 14qter, encompassing 23 genes. Genomic instability was evidenced by the presence of micronuclei and aneuploidies involving the ring and other chromosomes. CONCLUSION: The clinical features of our patient closely resembled those observed in other individuals with ring chromosome 14 syndrome. The most important point was that we were able to verify an instability of the r(14) chromosome, mainly involving anaphasic lags and its exclusion from the nucleus in the form of a micronucleus.

Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients.

BACKGROUND: Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1-4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans. METHODS: To understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and mutational analysis of CTSC were assayed in nine PLS patients and their relatives. Frequencies of CTSC gene polymorphisms and HLA alleles were determined in these patients, their relatives, and the population. RESULTS: Patients showed normal CTSC gene expression, but a deep reduction (up to 85%) in enzymatic activity in comparison to unrelated healthy individuals. A novel loss-of-function mutation, c.203 T > G (p.Leu68Arg), was found in all patients, and some carried the polymorphism c.458C > T (p.Thr153Ile). Allelic frequencies in patients, relatives and controls were 88.89%, 38.24% and 0.25% for G (c.203 T > G); and 11.11%, 8.82% and 9.00% for T (c.458C > T). HLA-DRB1*11 was found significantly more frequent (P = 0.0071) in patients than controls (33.33% vs. 7.32%), with an estimated relative risk of 6.33. CONCLUSIONS: The novel loss-of function mutation of CTSC gene (c.203 T > G) found in patients correlated with their diminished enzymatic activity, and HLA-DRB1*11 was found to be associated with PLS. The study of more PLS patients may give more insights into the etiology of the disease as well as its prevalence in México.

Correction: Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

[This corrects the article DOI: 10.1371/journal.pntd.0009145.].

Expression Analysis of miRNAs and Their Potential Role as Biomarkers for Prostate Cancer Detection.

Prostate cancer (PCa) is the second most frequent cancer diagnosed in men worldwide. The detection methods for PCa are either unreliable, like prostate-specific antigen (PSA), or extremely invasive, such as in the case of biopsies. Therefore, there is an urgent necessity for reliable and less invasive detection procedures that can differentiate between patients with benign diseases and those with cancer. In this matter, microRNAs (miRNAs) are suggested as potential biomarkers for cancer. MiRNAs have been found to be dysregulated in several different cancers, and these genetic alterations may present specific signatures for a given malignancy. Here, we examined the expression of miR141-3p, miR145-5p, miR146a-5p, and miR148b-3p in human tissue samples of PCa (n = 41) and benign prostatic diseases (BPD) (n = 30) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We combined the expression results with patient clinicopathological characteristics in logistic regression models to create accurate PCa predictive models. A model including information of miR148b-3p and patient age showed relevant prediction results (area under the curve [AUC] = 0.818, precision = 0.763, specificity = 0.762, and accuracy = 0.762). A model including all four miRNAs and patient age presented outstanding prediction results (AUC = 0.918, precision = 0.861, specificity = 0.861, and accuracy = 0.857). Our results represent a potential novel procedure based on logistic regression models that utilize miRNA expressions and patient age to assist with PCa diagnosis.

Altered Expression of Survivin Variants S-2B and S-WT in Breast Cancer Is Related to Adipokine Expression.

Breast cancer (BCa) is one of the leading causes of death in women with these types of malignancies. Early detection is pivotal to improve prognosis and reduce mortality. Several proteins and genes have been proposed as biomarkers for cancer; however, further studies are required before a molecule is accepted as a definitive biomarker. This study was aimed at investigating the expression of survivin variants S-WT, S-2B, and S-ΔEx3, as well as adipokines LEP and ADIPOQ in breast cancer. Breast samples were obtained from patients with (n = 27) and without (n = 20) BCa, and relative gene expression was assessed by RT-qPCR. S-WT and S-2B showed a significant increase in BCa samples (p = 0.005 and p = 0.001, respectively) and in high-aggressiveness BCa (p = 0.026 and p = 0.037, respectively). Despite S-ΔEx3 expression remained globally unchanged, when dividing BCa samples according to the stage, this gene showed a significant tendency to increase towards more advanced stages, and the exact opposite effect was observed for LEP. Furthermore, LEP expression showed a negative correlation with S-2B (p = 0.005) and S-WT (p = 0.011), and in the same manner, ADIPOQ was negatively related with these two survivin variants (p = 0.001 and p = 0.005, respectively). Interestingly, S-ΔEx3 expression appears unaffected by LEP and ADIPOQ expressions. Our results highlight the importance of investigating specific variants of a given gene, as sequence variation may grant different correlation with other important structures and diseases.

Novel TINF2 gene mutation in dyskeratosis congenita with extremely short telomeres: A case report.

BACKGROUND: Dyskeratosis congenita is a rare disease characterized by bone marrow failure and a clinical triad of oral leukoplakia, nail dystrophy, and abnormal skin pigmentation. The genetics of dyskeratosis congenita include mutations in genes involved in telomere maintenance, including TINF2. CASE SUMMARY: Here, we report a female patient who presented thrombocytopenia, anemia, reticulate hyperpigmentation, dystrophy in fingernails and toenails, and leukoplakia on the tongue. A histopathological study of the skin showed dyskeratocytes; however, a bone marrow biopsy revealed normal cell morphology. The patient was diagnosed with dyskeratosis congenita, but her family history did not reveal significant antecedents. Whole-exome sequencing showed a novel heterozygous punctual mutation in exon 6 from the TINF2 gene, namely, NM_001099274.1:c.854delp.(Val285Alafs*32). An analysis of telomere length showed short telomeres relative to the patient's age. CONCLUSION: The disease in this patient was caused by a germline novel mutation of TINF2 in one of her parents.

Incidence, Mortality, and Trends of Prostate Cancer in Mexico from 2000 to 2019: Results from the Global Burden of Disease Study 2019.

In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th most common cause of death globally in males. In Mexico, PC epidemiology has been studied by a number of metrics and over various periods, although without including the most up-to-date estimates. Herein, we describe and compare the burdens and trends of PC in Mexico and its 32 states from 2000 to 2019. For this study, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rates (ASR per 100,000 people) of the incidence and mortality of PC. In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6-36.0 thousand) incident cases and 9.2 thousand (7.7-12.7 thousand) deaths in males of all ages in 2019. Among the states, Sinaloa had the greatest ASR of incidence, and Guerrero had the highest mortality. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest.

Intra-host genetic population diversity: Role in emergence and persistence of drug resistance among Mycobacterium tuberculosis complex minor variants.

Drug resistant tuberculosis (DR-TB) is an important public health issue in different parts of the world. Mycobacterium tuberculosis complex variants (MTBC vars) preferentially infect certain hosts, limiting their distribution to different ecosystems. However, MTBC vars can infect other hosts beyond their preferred target potentially contributing to persistence of drug resistance (DR) in other niches. Here, we performed a comprehensive intra-host genetic analysis for the identification of DR-related mutations among all MTBC minor vars whole genome sequences (8,095 strains) publicly available worldwide. High confidence drug-resistance mutations in katG (isoniazid), rpsL (streptomycin), pncA (pyrazinamide), rpoB (rifampicin) and gyrA (fluoroquinolones) genes were identified among intrahost minor sub-populations in 197 different strains (2.43%) belonging to vars africanum, bovis, caprae, microti, orygis and pinnipedii. In addition, a three-dimensional structure modeling analysis to assess the role of novel mutations was also performed. Our findings highlight the importance of detecting discrete intra-host populations carrying DR mutations.

Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

Identifying the Mycobacterium tuberculosis resistance mutation patterns is of the utmost importance to assure proper patient's management and devising of control programs aimed to limit spread of disease. Zoonotic Mycobacterium bovis infection still represents a threat to human health, particularly in dairy production regions. Routinary, molecular characterization of M. bovis is performed primarily by spoligotyping and mycobacterial interspersed repetitive units (MIRU) while next generation sequencing (NGS) approaches are often performed by reference laboratories. However, spoligotyping and MIRU methodologies lack the resolution required for the fine characterization of tuberculosis isolates, particularly in outbreak settings. In conjunction with sophisticated bioinformatic algorithms, whole genome sequencing (WGS) analysis is becoming the method of choice for advanced genetic characterization of tuberculosis isolates. WGS provides valuable information on drug resistance and compensatory mutations that other technologies cannot assess. Here, we performed an analysis of the most frequently identified mutations associated with tuberculosis drug resistance and their genetic relationship among 2,074 Mycobacterium bovis WGS recovered primarily from non-human hosts. Full-length gene sequences harboring drug resistant associated mutations and their phylogenetic relationships were analyzed. The results showed that M. bovis isolates harbor mutations conferring resistance to both first- and second-line antibiotics. Mutations conferring resistance for isoniazid, fluoroquinolones, streptomycin, and aminoglycosides were identified among animal strains. Our findings highlight the importance of molecular surveillance to monitor the emergence of mutations associated with multi and extensive drug resistance in livestock and other non-human mammals.

Cytogenomic characterization of a de novo 4q34.1 deletion in a girl with mild dysmorphic features and a coagulation disorder.

BACKGROUND: 4q deletion syndrome is a rare chromosomal disorder that mostly arises de novo. The syndrome is characterized by craniofacial dysmorphism, digital abnormalities, skeletal alterations, heart malformations, developmental delay, growth retardation, Pierre Robin sequence, autistic spectrum and attention deficit-hyperactivity disorder, although not every patient shows the same features. Array comparative genomic hybridization (aCGH) use improves the detection of tiny chromosomal deletions and allows for a better understanding of genotype-phenotype correlations in affected patients. We report the case of a 6-year-old female patient showing mild dysmorphic features, mild mental disabilities and a coagulation disorder as a consequence of a de novo del(4)(q34.1) characterized by aCGH. CASE PRESENTATION: A 6-year-old female patient exhibited special craniofacial features, such as backward-rotated ears, upslanted palpebral fissures, broad nasal bridges, anteverted nares, broad nasal alae, smooth philtrums, smooth nasolabial folds, thin lips, horizontal labial commissures, and retrognathia. In the oral cavity, maxillary deformation, a high arched palate, agenesis of both mandibular canines and fusion of two mandibular incisors were observed. She also displayed bilateral implantation of the proximal thumbs, widely spaced nipples, dorsal kyphosis, hyperlordosis, and clitoral hypertrophy. In addition, the patient presented with coagulopathy, psychomotor delay, attention deficit-hyperactivity disorder, and mild mental disability. A chromosomal study showed the karyotype 46,XX,del(4)(q34.1), while an aCGH analysis revealed an 18.9 Mb deletion of a chromosome 4q subtelomeric region spanning 93 known genes. CONCLUSION: The clinical manifestations of this patient were similar to those reported in other individuals with 4q deletion syndrome. Although most of the patients with a 4q34 terminal deletion share similarities, variations in phenotype are also common. In general, clinical effects of chromosomal deletion syndromes depend on the length of the deleted chromosomal segment and, consequently, on the number of lost genes; however, in all of these syndromes, there is no simple correlation between the phenotype and the chromosomal region involved, particularly in cases of 4q deletion.

Prevalence of UGT1A1 (TA)n promoter polymorphism in Panamanians neonates with G6PD deficiency.

A relationship between the polymorphism in promoter region of the UGT1A1 gene and the development of jaundice has been demonstrated recently. This polymorphism leads to 30% of normal rate transcription initiation of UGT1A1 gene, thus decreasing the bilirubin glucuronidation. The combination of the G6PD deficiency and polymorphism in neonates and adults may causepronounced hyperbilirubinaemias. The aim of this study was to analyse the variations in the UGT1A1 gene promoter in Panamanians neonates with G6PD deficiency and its association with neonatal jaundice (NJ). We identified five different genotypes of TA repeats, in 17 neonates (42.5%) the normal variant TA6/TA6 and in the other 57.5% of the subjects: TA7/TA7 (12.5%), TA6/TA7 (40%), TA6/TA8 (2.5%) and TA6/TA5 (2.5%). Additionally 75% of the 16 newborns that showed NJ had an abnormal variant in the promotersequence, although, there was no significant difference (P = 0.068). The risk of jaundice in neonates with TA7 variant was thrice higher in subjects than with other alleles (P = 0.093, CI: 0.81-11.67). The TA7 allele frequency in this study (0.325) was consistent with the global frequency and similar to Caucasians. The results proved that there is no significant relationship between promoter polymorphism in UGT1A1 and NJ in G6PD deficient Panamanian newborns. Further studies with a greater number of subjects would determine the exact relationship between marked NJ and UGT1A promoter variations.

Underexpression of circulating miR-145-5p and miR-133a-3p are associated with breast cancer and immunohistochemical markers.

BACKGROUND: MicroRNAs (miRNAs) are involved in the regulation of genes with important roles in cancer. Therefore, they represent interesting targets as biomarkers for early detection, follow-up, and prognosis of the disease. CONTEXT: In early stages of breast cancer, differences in the expression of miR-148b-3p, miR-145-5p and miR-133a-3p have been reported. AIMS: To compare the expression of miR-148b-3p, miR-145-5p and miR-133a-3p in serum samples from female patients with and without breast cancer. SETTING AND DESIGN: Case control study. MATERIALS AND METHODS: We quantified the expression by real-time polymerase chain reaction of miR-148b-3p, miR-145-5p, and miR-133a-3p in serum samples from 27 breast cancer (BC) and 17 benign breast tumor patients. STATISTICAL ANALYSIS USED: Comparison between groups with categorical variables was made using the Pearson's Chi-square test. Comparative analysis for continuous variables between two groups was performed using the Student's t-test. One-way analysis of variance (ANOVA) was used for multigroup comparison, followed by Tukey HSD analysis. RESULTS: The use of contraceptives and a high number of births were identified as risk factors for BC. We observed that miR-145-5p expresses in low levels in BC and positively diagnosed Her2 patients. In addition, BC patients with either ductal carcinoma or positive molecular diagnosis for estrogen receptor, progesterone receptor, luminal A, or Her2 negative, presented a decreased expression of miR-133a-3p. CONCLUSIONS: We observed an existing association between the molecular characteristics of BC and levels of circulating miR-133a-3p and miR-145-5p, proving the potential role of miRNAs as biomarkers for BC.

Promoter polymorphisms of the PCA3 gene are not associated with its overexpression in prostate cancer patients.

In male, the prostate cancer (PCa) is one of the most frequent neoplasias and the second cause of cancer deaths worldwide. In 2015, more than 6000 men died in Mexico due to this disease. In this regard, prostate cancer associated gene 3 (PCA3) has become an interesting target in PCa as is found highly overexpressed. Moreover, TAAA tandem repeats have been suggested to be associated with the regulation of PCA3 expression and, in turn, to be related with the development of the disease. The aim of the study was to understand thegenetic basis of the disease in search for a better diagnosis. Expression levels of PCA3 gene were analysed in tissue of 13 patients diagnosed with PCa and six patients diagnosed with a benign prostatic disease (BPD). The absolute expression of PCA3 was quantified by real-time PCR. Genotype for TAAA tandem repeats was measured using automatic sequencing and the results were analysed to determine whether an association existed between them. We identified three alleles: 4, 5, 6 and four genotypes: 4/5, 5/5, 5/6, 6/6. Our analysis identified amutation in the nucleotide 76764237 of the PCA3 gene that generates an extra TAAA tandem repeat. The nucleotide mutation is present in 61.53% of PCa and 66.66% of BPD patients. Our study revealed the presence of a mutation in the PCA3 gene that generates an extra TAAA tandem. We observed no association between the absolute expression of PCA3 messenger and the number of TAAA repetitions.

Report of trisomy 2q34-qter and monosomy 4q35.2-qter in a child with mild dysmorphic syndrome and karyotype 46,XY,der(4)t(2;4)(q34;q35.2)pat.

BACKGROUND: Concomitant trisomy 2q3 and monosomy 4q3 have been rarely reported. Pure trisomy 2q3 has been associated with microcephaly, hypertelorism, low-set ears, micrognathia, visceral abnormalities, and growth retardation. Monosomy 4q3 includes a wide variety of dysmorphic features such an abnormal skull shape, hypertelorism, Pierre Robin sequence, short nose with abnormal bridge, fifth finger clinodactyly, congenital heart, and genitourinary defects, in addition to intellectual disability, developmental delay, and hypotonia, but more distal deletions involving 4q34-qter may result in milder phenotypes. Here, we present a child with a mild dysmorphic syndrome, resulted of a duplication 2q34-qter and a deletion 4q35.2-qter inherited of his father. CASE PRESENTATION: We report a child, who at birth presented hypotonia, dysmorphism, and bilateral cryptorchidism. At 2 years and 9 month of age he showed brachycephaly, narrow forehead, bilateral frontoparietal hypertrichosis, down slanting palpebral fissures, sparse eyebrows, sparse short eyelashes, hypertelorism, depressed nasal root, broad nasal bridge, bulbous nasal tip, prominent colummela, broad nasal ala, smooth filtrum, high arched palate, thin upper lips, and ears rotated backwards. He also showed telethelia, hypertrichosis from dorsal to the sacral region, hands with clinodactyly and hypoplasia of the terminal phalanx of the fifth finger, and broad thumbs, broad first toes, and right cryptorchidism. A chromosomal study revealed a karyotype 46,XY,der(4)t(2;4)(q34;q35.2), while an array comparative genomic hybridization showed a 31.12 Mb duplication of the chromosome 2q34-q37.3 and a 1.49 Mb deletion in the chromosome 4q35.2. CONCLUSIONS: To our knowledge, only four families with translocation t(2;4) have been reported, two of them involving t(2q;4q), but the breakpoints involved in our patient have not been previously observed. The genomic imbalance in this patient was a duplication of 318 genes of the region 2q34-q37.3 and a deletion of 7 genes of 4q35.2. We discuss difficulty to assign specific congenital abnormalities to these duplicated/deleted regions and include some cases with terminal deletions of 4q with normal or just mildly detectable phenotypic effects.