Searching chromosome mosaicisms in 45, X Turner syndrome: how relevant is it?

ABSTRACT Objective: To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS). Materials and methods: FISH and PCR were performed for the presence of chromosome mosaicism and Y-derived-material and genetic findings were correlated to clinical data. Results: Thirty-one participants were enrolled: 18 (58%) had chromosome mosaicisms (FISH), Y-derived material was found in 2. Yet, SRY primer was found with PCR in only one of them and DYZ3 was not found. The most frequent clinical findings were short or webbed neck (81,82%), high-arched palate (78%), breast hypertelorism, e cubitus valgus and genu valgus (57.6%, both), short fourth metacarpals (46.9%), epicanthic folds (43.8%), shield chest (43.8%), lymphedema (37.5%), and low set ears (34.4%). Both patients with Y-derived-material had primary amenorrhea, dyslipidemia and reached the height of 150 cm despite not treated with recombinant growth hormone (GHr). One of them showed 26% of leukocytes with Y-derived material and few clinical findings. Conclusions: FISH techniques proved efficient in detecting chromosome mosaicisms and Y-derived material and searching in different tissues such as mouth cells is critical due to the possibility of tissue-specific mosaicism. Phenotypical variance in TS may be a signal of chromosome mosaicisms, especially with the presence of Y-derived material.

Treze anos de análises citogenéticas no Laboratório de Genética Médicado Hospital Universitário Professor Edgard Santos / Thirteen years of cytogenetic analysis at Laboratory of Medical Genetics of University Hospital Professor Edgard Santos

Introdução: as anormalidades cromossômicas constituem uma das maiores categorias de doenças genéticas e são causa significativa de deficiência intelectual, déficit pôndero-estatural, malformações congênitas e dismorfismos faciais. Este trabalho é um estudo retrospectivo longitudinal de análises cromossômicas realizadas no Laboratório de Genética Médica do Complexo Hospitalar Universitário Professor Edgard Santos (UFBA). Objetivos: identificar os motivos de encaminhamento, os resultados citogenéticos do público atendido entre 2005 e 2017, e a taxa de diagnóstico etiológico obtido pelo cariótipo e pela FISH. Metodologia: foram encaminhados 3.863 pacientes, com suspeita clínica de cromossomopatias. As análises genéticas foram realizadas a partir de cultura de linfócitos e posterior bandamento G e/ou Hibridação in situ por fluorescência (FISH). Os dados dos pacientes foram obtidos através das fichas de encaminhamento e das análises cromossômicas. Resultados: o principal motivo de encaminhamento foi dismorfologias e/ou deficiência intelectual seguida de suspeita da Síndrome de Down e Síndrome de Turner, confirmadas em 14% e 4% da amostra, respectivamente. Foi possível concluir o diagnóstico etiológico em 904 casos (24,5%). Discussão: a confirmação etiológica das anomalias congênitas é extremamente importante para o prognóstico do paciente, sendo necessário investimentos em testes citomoleculares, como a FISH e o microarray, visando ampliar a taxa de diagnóstico. Conclusão: o cariótipo Banda G concluiu o diagnóstico clínico em 23.3% dos pacientes, compatível com a frequência das síndromes mais comumente diagnosticadas por esse teste, enquanto que a FISH conseguiu adicionar diagnóstico etiológico em mais 1,2% dos casos, esses envolvidos com as síndromes de microdeleções.

Introduction: chromosomal abnormalities constitute one of the major categories of genetic diseases and are a significant cause of intellectual deficiency, weight deficit, congenital malformations and facial dysmorphisms. This work is a retrospective longitudinal study of chromosomal analysis performed at the Laboratory of Medical Genetics of the University Hospital Complex Professor Edgard Santos (UFBA). Objectives: to identify the referral motives, the cytogenetic results of the public served between 2005 and 2017, and the etiological diagnosis rate obtained by the karyotype and FISH. Methodology: 3,863 patients were referred, with clinical suspicion of chromosomal disorders. Genetic analyzes were performed from lymphocyte culture and subsequent G banding and / or fluorescence in situ hybridization (FISH). Patient data were obtained through referral forms and chromosome analysis. Results: the main reason for referral was dysmorphologies and / or intellectual disability followed by Down Syndrome and Turner Syndrome, confirmed in 14% and 4% of the sample, respectively. It was possible to conclude the etiological diagnosis in 904 cases (24.5%). Discussion: the etiologic confirmation of congenital anomalies is extremely important for the prognosis of the patient, and investments in cyto-molecular tests, such as FISH and microarray, are necessary to increase the diagnostic rate. Conclusion: the G-band karyotype concluded the clinical diagnosis in 23.3% of the patients, compatible with the frequency of syndromes most commonly diagnosed by this test, while FISH was able to add an etiological diagnosis in another 1.2% of cases, those involved with microdeletion syndromes