Turner syndrome (TS) is a common genetic disorder in females associated with the absence of complete or parts of a second sex chromosome. In 5-12% of patients, mosaicism for a cell line with a normal or structurally abnormal Y chromosome is identified. The presence of Y-chromosome material is of medical importance because it results in an increased risk of developing gonadal tumours and virilisation. Molecular study and fluorescence in situ hybridisation approaches were used to study 74 Brazilian TS patients in order to determine the frequency of hidden Y-chromosome mosaicism, and to infer the potential risk of developing malignancies. Additionally, we describe one TS girl with a very uncommon karyotype 46,X,der(X)t(X;Y)(p22.3?2;q11.23) comprising a partial monosomy of Xp22.3?2 together with a partial monosomy of Yq11.23. The presence of cryptic Y-chromosome-specific sequences was detected in 2.7% of the cases. All patients with Y-chromosome-positive sequences showed normal female genitalia with no signs of virilisation. Indeed, the clinical data from Y-chromosome-positive patients was very similar to those with Y-negative results. Therefore, we recommend that the search for hidden Y-chromosome mosaicism should be carried out in all TS cases and not be limited to virilised patients or carriers of a specific karyotype.
ABSTRACT. Turner syndrome (TS) is a chronic disease related to haploinsufficiency of genes that are normally expressed in both X chromosomes in patients with female phenotype that is associated with a wide range of somatic malformations. We made detailed cytogenetic and clinical analysis of 65 patients with TS from the region of Recife, Brazil, to determine the effects of different chromosome constitutions on expression of the TS phenotype. Overall, patients with X-monosomy exhibited a tendency to have more severe phenotypes with higher morbidity, showing its importance in TS prognosis. Additionally, we found rare genetic and phenotypic abnormalities associated with this syndrome. To the best of our knowledge, this is the first case of 45,X,t(11;12)(q22;q22) described as a TS karyotype. Turner patients usually have normal intelligence; however, moderate to severe levels of mental retardation were found in 5 TS cases, which is considerate a very uncommon feature in this syndrome.
Turner syndrome (TS) is characterized by a set of clinical conditions, including autoimmune/inflammatory diseases and infectious conditions, that can compromise a patient’s quality of life. Here we assessed polymorphisms in CTLA-4 +49A/G (rs231775), PTPN22 +1858G/A (rs2476601), and MBL2 -550 (H/L) (rs11003125), -221(X/Y) (rs7096206) and exon 1 (A/O) in women from northeastern Brazil to determine whether polymorphisms within these key immune response genes confer differential susceptibility to clinical conditions in TS. A case-control genetic association study was performed, including 86 female TS patients and 179 healthy women. An association was observed for the A/G genotype of CTLA-4 +49A/G in TS patients (p=0.043, odds ratio [OR]=0.54). In addition, an association between the CTLA-4 G/G genotype and obesity was detected in TS patients (p=0.02, OR=6.04). Regarding, the -550(H/L) polymorphism in the MBL2 promoter, the frequency of the H/L genotype was significantly higher in the TS group than healthy controls (p=0.01, OR=1.96). The H/H genotype indicated a protective effect in TS patients (p=0.01, OR=0.23). No differences were observed in the distribution of -221(X/Y), MBL2 exon 1 variants, and PTPN22 +1858G/A in any assessed groups. CTLA-4 variants are potentially involved in obesity in this cohort of TS patients from northeastern Brazil.
A existência de mosaicismo cromossômico tem sido apontada como um fator determinante para a viabilidade das pacientes portadoras da Síndrome de Turner (ST), tendo em vista que apenas 1% dos fetos com o cariótipo 45,X são nativivos, pois 99% são abortados espontaneamente Diversos casos de mosaicismo cromossômico têm sido descritos, com as mais variadas constituições celulares associadas à linhagem clássica para a ST (45,X). Essa coexistência de linhagens pode resultar na maior parte dos casos no abrandamento dos sintomas que caracterizam a síndrome, sendo as consequências fenotípicas decorrentes do mosaicismo dependentes da proporção de células alteradas Esse estudo teve como objetivo determinar a prevalência de mosaicismo cromossômico em portadores da Síndrome de Turner e verificar possíveis associações entre os fenótipos e cariótipos dessas pacientes oriundas do Estado de Pernambuco. Para o desenvolvimento da investigação foram coletadas amostras de sangue periférico em pacientes que foram recrutadas do Serviço de Genética Médica do Instituto Materno Infantil Prof. Fernando Figueira (IMIP) e Serviço de Endocrinologia Pediátrica do Hospital das Clínicas (HC), entre outubro de 2006 e agosto de 2016. O cultivo de linfócitos de sangue periférico foi realizado para cada paciente e, posteriormente, um bandeamento G foi utilizado para identificação cromossômica e detecção das alterações encontradas. A análise citogenética detectou cariótipos compatíveis com a ST em 84 pacientes, O cariótipo 45,X foi observado em 58,3% da amostra, seguido de indivíduos portadores de mosaicismo, que representaram 33,3% dos casos. Entre as pacientes portadoras de mosaicismo, o cariótipo 46,X,i(Xq)/45,X foi o mais prevalente, representando 16,6% da amostra. Linhagens celulares contendo cromossomo em anel (46,X,r(X)/45,X) e o cromossomo Y (45,X/46,XY) também foram detectadas. As manifestações clínicas mais incidentes nas pacientes com ST foram a baixa estatura e amenorréia primária, sendo constatado a ocorrência de 89,2% e 64,3%, respectivamente, em pacientes com mosaicismo confirmado. Os resultados obtidos confirmaram a necessidade de investigação de mosaicismo cromossômico, para determinar uma relação entre a expressão fenotípica específica e cada tipo de associação de linhagens cromossômicas diferentes. Além disso, a avaliação precisa da constituição cromossômica irá proporcionar às portadoras da ST um diagnóstico conclusivo, prognóstico adequado e tratamento com terapias específicas.Auxílio financeiro: FACEPE, UFPE
Folate metabolism dysfunction can lead to DNA hypomethylation and abnormal chromosomal segregation. Previous investigations of this association have produced controversial results. Here we performed a case-control study in patients with Turner syndrome (TS) to determine the effects of genetic polymorphisms of folate pathway genes as potential risk factors for somatic chromosomal nondisjunction. TS is a useful model for this investigation because patients with TS show a high frequency of chromosome mosaicism. Here we investigated the possible association of polymorphisms of the MTHFR gene with TS risk, which has been previously investigated with controversial results. We also examined the effects of MTR, RFC1, and TYMS gene polymorphisms in TS for the first time. The risk was evaluated according to allelic and genotype (independent and combined) frequencies among 70 patients with TS and 144 age-matched healthy control subjects. Polymorphism genotyping was performed by PCR, PCR-RFLP, and PCR-ASA. The polymorphisms MTHFR 677C>T and 1298A>C, MTR 2756A>G, RFC1 80G>A, and TYMS 2R/3R-alone or in combinations-were not associated with the risk of chromosomal aneuploidy in TS. In conclusion, our present findings did not support a link between impaired folate metabolism and abnormal chromosome segregation leading to somatic nondisjunction in TS patients.
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