5p13. 2 Chromosomal duplication syndrome: case report and literature review / Síndrome de duplicação cromossômica 5p13. 2: relato de caso e revisão da literatura

Chromosome 5p13 duplication syndrome represents a contiguous gene syndrome involving duplication of several genes on chromosome 5p13. Some clinical phenotypes are related to it, such as: obsessive-compulsive behavior, small palpebral fissures, intellectual disability, global development delay and ocular hypertelorism. The exact mechanism behind these changes has not well known and further studies are needed for this purpose. Since it is a rare and uncommon clinical situation, the case report contributes to the knowledge of the disease and early diagnosis. This condition mainly affects the cognitive neuromuscular system. We describe an 8-year-old Brazilian patient with the duplication of chromosome 5p13.2, karyotype, whose neurodevelopmental evaluation presented cognitive impairment, severe language delay and atypical physical examination, with ocular hypertelorism, right auricular tags, congenital heart defect and long fingers. The patient was diagnosed by comparative genomic hybridization (CGH)-array revealing a 204Kb of DNA duplication. The exact mechanism behind these structural disorders is still unclear and further studies are needed for this purpose. Nevertheless, the diagnostic suspicion of this genetic alteration that, in general, presents late diagnosis, should be considered to enable better clinical support to the patients and family genetic counseling.

A síndrome da duplicação do cromossomo 5p13 representa uma síndrome genética contígua envolvendo a duplicação de vários genes contidos nesta região. Alguns fenótipos clínicos estão relacionados com ela, tais como: comportamento obsessivo compulsivo, fissuras palpebrais pequenas, déficit intelectual, atraso no desenvolvimento global e hipertelorismo ocular. Por ser uma situação clínica rara, o relato do caso contribui para a disseminação do conhecimento acerca da condição, assim como para seu diagnóstico precoce. Descrevemos uma paciente brasileira de oito anos com a duplicação do cromossomo 5p13.2, que na avaliação do neurodesenvolvimento apresentou comprometimento cognitivo, grave atraso da linguagem e dismorfismos como hipertelorismo ocular, apêndice auricular direito, sopro cardíaco, relacionado a defeito do septo ventricular, e dedos alongados. A paciente foi diagnosticada por meio da pesquisa molecular (CGH)-array com ganho de 204Kb de DNA. O mecanismo exato por trás dessas alterações estruturais ainda não está claro e são necessários mais estudos para este fim. Não obstante, a suspeita diagnóstica dessa alteração genética que, em geral, apresenta diagnóstico tardio, deve ser aventada para viabilizar melhor suporte clínico aos pacientes e aconselhamento genético familiar.

A Case of Acute Myeloid Leukemia with Bone Marrow Basophilia and Dysmegakaryocytic Hyperplasia with Isochromosome 17q as a Sole Cytogenetic Abnormality: A Clinical Study with Literature Review

A new clinico-pathological entity in which isochromosome 17q is the sole abnormality has been reported in myelodysplastic syndrome and in myeloproliferative neoplasm with an aggressive course; In particular, myelodysplastic syndrome with the isolated i(17)(q10) chromosome has the unique features of male sex, severe anemia, dysmegakaryocytic hyperplasia, increased micromegakaryocytes, basophilia, eosinophila and high risk for progression to acute myeloid leukemia (AML). However, the isolated i(17)(q10) is occurring at a relatively low frequency in de novo AML, and only a few reports are available in the literature about the clinical features and molecular characteristics of the isolated i(17)(q10) in AML. Herein, we report both the clinico-pathological features and the results of high resolution single nucleotide polymorphism (SNP) array analysis in a case of AML with i(17)(q10) as the sole cytogenetic abnormality. This case showed marrow findings of basophilia and dysmegakaryocytic hyperplasia and aggressive clinical outcome and these findings were suggestive of the presence of underlying myelodysplastic syndrome. The breakpoint of i(17)(q10) was located within 17p11.2 sub-band, which is known as a genetically highly unstable region presenting a unique genomic architectural features of low copy repeats (LCRs); thus, LCRs within 17p11.2 might lead to genomic instability and facilitate somatic genetic rearrangements such as i(17) (q10) and could play an important pathogenetic role in presenting unique clinico-pathologic features as well as in tumor development and disease progression.

TP53 PIN3 polymorphism associated with breast cancer risk in Iranian women.

Background: Breast cancer is one of the most common cancers in Iranian women. The p53 gene plays a principal role in genomic stability, and its function varies according to polymorphisms. The aim of our study was to determine the relationship between the intron3 16bp duplication polymorphism of the p53 gene and breast cancer in Iranian women. Materials and Methods: We performed a case-control study among 145 patients with invasive ductal carcinoma of the breast and 145 controls in Isfahan, Iran. The distribution of the intron3 16bp duplication polymorphism was determined by polymerase chain reaction (PCR). The relationship between clinicopathological data and the PIN3 polymorphism was examined using chi-squared analysis. Results: A significant difference was observed in the polymorphism variants in breast cancer specimens compared with controls (P < .001). Among the cancer patients, 59.9% were below the age of 50 years; and 67.5% of the patients in this group had the intron3 16bp duplication polymorphism. Conclusions: PIN3 Ins 16bp duplication polymorphism is a genetically predisposing factor for breast cancer development in Iranian women and may be causal in patients under the age of 50 years.

Non-Synteny Regions in the Human Genome

Closely related species share large genomic segments called syntenic regions, where the genomic elements such as genes are arranged co-linearly among the species. While synteny is an important criteria in establishing orthologous regions between species, non-syntenic regions may display species-specific features. As the first step in cataloging human- or primate-specific genomic elements, we surveyed human genomic regions that are not syntenic with any other non-primate mammalian genomes sequenced so far. Based on the data compiled in Ensembl databases, we were able to identify 10 such regions located in eight different human chromosomes. Interestingly, most of these highly human- or primate-specific loci are concentrated in subtelomeric or pericentromeric regions. It has been reported that subtelomeric regions in human chromosomes are highly plastic and filled with recently shuffled genomic elements. Pericentromeric regions also show a great deal of segmental duplications. Such genomic rearrangements may have caused these large human- or primate-specific genome segments.

Understanding of epigenetics and dna methylation