Variable Phenotypes of Epilepsy, Intellectual Disability, and Schizophrenia Caused by 12p13.33-p13.32 Terminal Microdeletion in a Korean Family: A Case Report and Literature Review.

A simultaneous analysis of nucleotide changes and copy number variations (CNVs) based on exome sequencing data was demonstrated as a potential new first-tier diagnosis strategy for rare neuropsychiatric disorders. In this report, using depth-of-coverage analysis from exome sequencing data, we described variable phenotypes of epilepsy, intellectual disability (ID), and schizophrenia caused by 12p13.33-p13.32 terminal microdeletion in a Korean family. We hypothesized that CACNA1C and KDM5A genes of the six candidate genes located in this region were the best candidates for explaining epilepsy, ID, and schizophrenia and may be responsible for clinical features reported in cases with monosomy of the 12p13.33 subtelomeric region. On the background of microdeletion syndrome, which was described in clinical cases with mild, moderate, and severe neurodevelopmental manifestations as well as impairments, the clinician may determine whether the patient will end up with a more severe or milder end-phenotype, which in turn determines disease prognosis. In our case, the 12p13.33-p13.32 terminal microdeletion may explain the variable expressivity in the same family. However, further comprehensive studies with larger cohorts focusing on careful phenotyping across the lifespan are required to clearly elucidate the possible contribution of genetic modifiers and the environmental influence on the expressivity of 12p13.33 microdeletion and associated characteristics.

Role of the 12q24.12 locus in the onset of preeclampsia: an Italian case-control study.

OBJECTIVE: The 12q24.12 locus has been reported to be involved in the control of many traits and also in severe diseases such as cardiovascular disease, hypertension and some immune-related disease. To our knowledge, no study has been published so far investigating the role of this locus in the pathogenesis of preeclampsia (PE). METHODS: We genotyped four single nucleotide polymorphisms (SNPs) in 12q24.12 locus in 198 preeclamptic, 224 chronic hypertensive and 265 normotensive women from Italy, to test the contribution polymorphisms/haplotypes on the onset of preeclampsia and their association with chronic hypertension. RESULTS: No association was observed for any single SNP, while a common haplotype CGTG (21% in normotensive women) revealed a possible protective effect (OR 0.64, 95% CI 0.42-0.97) against preeclampsia. CONCLUSIONS: Our data suggest that a common haplotype within 12q24.12 locus may be associated with a protective effect against preeclampsia. This observation may be linked with the potential role of this region in the control of microcirculation. To the best of our knowledge, our study is the first one that links the 12q24.12 locus with this life-threatening perinatal complication of unknown etiology. Further physiological and functional studies are needed to clarify the molecular mechanisms and pathways of preeclampsia.

Tumor miofibroblástico de vejiga / Miofibroblastic tumor of bladder

El tumor miofibroblásticos es un tumor mesenquimal benigno de carácter excepcional, siendo su localización mas habitual es el pulmón; mientras que su aparición en la vejiga, es excepcional, no existiendo mas de 100 casos publicados, de este tipo de tumor en la vejiga. Este tipo de tumor que clínica y radiológicamente, se comporta como un tumor maligno. El diagnóstico patológico es complejo, debido a su similitud con los sarcomas, siendo necesario recurrir a la inmunohistoquímica para un diagnostico de certeza. El tratamiento mediante resección amplia suele ser suficiente no existiendo en la actualidad ningún caso de metástasis a distancia, ni de malignizacion. Presentamos un nuevo caso de este tumor, realizando una amplia revisión bibliográfica (AU)

The miofibroblastic tumor, is a mesenchimal benign tumor of exceptional character, being its localization but habitual it is the lung; while its appearance in the bladder, is exceptional, not existing but of 100 published cases, of this tumor type in the bladder. This tumor type that clinic and radiologics, behave as a wicked tumor. The pathological diagnosis is complex, due to its similarity with the sarcomas, being necessary to appeal to the inmunohistoquimics for a I diagnose of certainty.The treatment by means of wide resection is usually enough not existing any case of metastasis at the present time at distance, neither of malignization. We present a new case of this neoplasm, carrying out a wide bibliographical revision (AU)

Immature teratoma of the pineal gland with isochromosome 12p.

An immature teratoma arising in the pineal gland in a 27-year-old male was shown to present an isochromosome 12p as evidenced by cytogenetic and fluorescence in situ hybridization analysis. As i(12p) is characteristic of gonadal germ cell tumors, this case indicates that similar genetic pathways may operate in gonadal and intracranial teratomas.

Chromosomes 8, 12, and 17 copy number in Astler-Coller stage C colon cancer in relation to proliferative activity and DNA ploidy.

Fluorescence in situ hybridization using centromere-specific DNA probes to chromosomes 8, 12, and 17 was applied to 23 archival paraffin-embedded stage C colonic cancer specimens. Chromosome copy number was related to flow cytometric determinations of S-phase fraction and DNA ploidy. Three to eight copies of chromosomes 8, 12, and 17 were observed at mean frequencies of 28.7%, 37.8%, and 20.9%, respectively. The mean frequency of multiple copies of chromosome 12 was significantly greater than that for chromosome 17 (P < 0.0025). The mean frequency of single copies of chromosome 17 was significantly greater than that for chromosomes 8 and 12 (P < 0.0025 and P < 0.0005, respectively). Regarding the fourth quartile of cases, defined on the basis of the frequency of multiple chromosome copies, the proportion demonstrating moderate to high proliferative activity greatly exceeded the proportion displaying low proliferative activity. The same cases (most chromosomally aberrant) also generally demonstrated DNA aneuploidy. The results indicate a substantial degree of karyotypic instability in advanced colon cancer, particularly in cases with high proliferative activity and DNA aneuploidy.

Clonal rearrangement of chromosome band 6p21 in the mesenchymal component of pulmonary chondroid hamartoma.

Pulmonary chondroid hamartomas (PCH) are biphasic benign tumors that contain both mesenchymal and epithelial populations. In this report we describe two PCH in which clonal translocations at chromosome band 6p21 were demonstrated in mesenchymal cells. One of these had a unique translocation, t(6;14)(p21;q24), that was also found in one of two PCH karyotyped previously. The t(6;14) has not been described in other varieties of benign or malignant neoplasia. The 6p21 aberrations are of particular interest because break points in this chromosomal region appear to be characteristic of endometrial polyps. Endometrial polyps, like PCH, are biphasic benign tumors in which mesenchymal clonality has been demonstrated.

Growth characteristics and response to growth hormone therapy in patients with hypochondroplasia: genetic linkage of the insulin-like growth factor I gene at chromosome 12q23 to the disease in a subgroup of these patients.

Hypochondroplasia, a heterogeneous and usually mild form of chondrodystrophy, is a common cause of short stature. It often goes unrecognized in childhood and is diagnosed in adult life when disproportionate short stature becomes obvious. We performed restriction enzyme analysis of the insulin-like growth factor I (IGF-I) gene on the families of 20 white British Caucasian children with short stature attributed to hypochondroplasia by radiological and clinical criteria, who were undergoing human growth hormone (r-hGH) treatment, in 60 children with isolated growth hormone deficiency and in 50 normal individuals. The frequency of the heterozygous pattern (Hind III: 8.2, 5.2, 4.8, 3.2 kb fragments, Pvu: 8.4, 5.1, 4.7, 2.5 kb fragments) in children with hypochondroplasia was significantly higher (chi2: P less than 0.05) than in the control groups. The hypochondroplastic children whose response to r-hGH treatment was characterized by a proportionate increase in both spinal and subischial leg length were all heterozygous for two co-inherited IGF-I gene restriction fragment length polymorphism (RFLP) alleles (Hind III: 5.2, 4.8 kb; Pvu II: 5.1, 4.7 kb). Children whose response was characterized by accentuation of the body disproportion by r-hGH treatment were all homozygous for these alleles (Hind III: 4.8, 4.8 kb; Pvu II: 4.7, 4.7 kb). Their response to r-hGH treatment is significantly different (P less than 0.01). Studies of the families of the heterozygous affected children demonstrated strong linkage (lod score 3.311 at zero recombination) of the IGF-I gene locus at chromosome 12q23 to this subgroup of hypochondroplasia. The 5.2 kb Hind III and 5.1 kb Pvu II alleles are in strong linkage disequilibrium with this trait. These data indicate that IGF-I gene may be a candidate gene for involvement in the aetiology of short stature presenting with hypochondroplastic features and a proportionate response to r-hGH treatment; they also provide support for the concept of genetic heterogeneity in chondrodystrophy.