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Intellectual disability (ID) is considered a common neuropsychiatric disorder that affects up to 3% of the population. The etiologic origin of ID may be genetic, environmental, and multifactorial. Chromosomopathies are relatively common among the genetic causes of ID, especially in the most severe cases and those associated with dysmorphic features. Currently, the application of new molecular cytogenetics technologies has increasingly allowed the identification of microdeletions, microduplications, and unbalanced translocations as causes of ID. The objective of this study was to investigate the etiology of ID in patients admitted to a public hospital in Northeastern Brazil. In total, 119 patients with ID who had normal karyotypes and fragile X exams participated in this study. The patients were initially physically examined for microdeletion syndromes and then tested using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), methylation-sensitive polymerase chain reaction (MS-PCR), and chromosome microarray analysis (CMA), according to clinical suspicion. Patients with no diagnoses after FISH, MLPA, and/or MS-PCR evaluations were subsequently tested by CMA. The rate of etiologic diagnoses of ID in the current study was 28%. FISH diagnosed 25 out of 79 tested (31%), MLPA diagnosed 26 out of 79 tested (32%), MS-PCR diagnosed 7 out of 20 tested (35%), and the single nucleotide polymorphism array diagnosed 6 out of 27 tested (22%). Although the CMA is the most complete and recommended tool for the diagnosis of microdeletions, microduplications, and unbalance translocations in patients with ID, FISH, MLPA, and MS-PCR testing can be used as the first tests for specific syndromes, as long as the patients are first physically screened clinically, especially in the public health networks system in Brazil, where resources are scarce.
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Approximately 30 sex chromosome discordant chimera cases have been reported to date. In particular, there are few reported cases of chimerism involving coexisting normal and abnormal lineages that each carries a distinct sex chromosome complement. To our knowledge, this is the first case of sexual chimerism with a simultaneous chromosomal aneuploidy involving chromosome 8. This report represents the data from 11 years of follow-up.
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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.
Assuntos
Humanos , Feminino , Síndrome de Turner/genética , Estatura , Reação em Cadeia da Polimerase , Cromossomos , MosaicismoRESUMO
OBJECTIVE: To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS). 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. CONCLUSION: 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.
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Síndrome de Turner , Estatura , Cromossomos , Feminino , Humanos , Mosaicismo , Reação em Cadeia da Polimerase , Síndrome de Turner/genéticaRESUMO
Prader-Willi syndrome (PWS) is one of the common neurogenetic disorders associated with intellectual disability. PWS involves a complex inheritance pattern and is caused by an absence of gene expression on the paternally inherited 15q11.2-q13 region, either due to deletion, maternal uniparental disomy or imprinting defect. The syndrome is characterized principally by severe neonatal hypotonia, a weak suck in infancy that is later followed by hyperphagia and obesity, developmental delay, intellectual disability and short stature. In the case of the chromosome 15q26-qter deletion syndrome or Drayer's syndrome, very few reports have been published. Its characteristics include intrauterine growth restriction, postnatal growth failure, varying degrees of intellectual disability, developmental delay, typical facial appearance and diaphragmatic hernia. The present paper describes a female patient in whom clinical findings were suggestive of PWS and deletion in the 15q26-qter region. Both karyotyping and methylation-specific polymerase chain reaction were shown to be normal. Nevertheless, fluorescence in situ hybridization showed a 15qter deletion that was later mapped by single nucleotide polymorphism (SNP)-array. The deleted genomic region involves the insulin-like growth factor-1 receptor (IGF1R) gene, which is related to short stature, developmental delay and intellectual disability. This case had various clinical characteristics in common with the cases of 15q26-qter deletionand characteristics compatible with PWS.
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Anormalidades Múltiplas/genética , Transtornos do Crescimento/genética , Deficiência Intelectual/genética , Microcefalia/genética , Síndrome de Prader-Willi/genética , Anormalidades Múltiplas/patologia , Feminino , Transtornos do Crescimento/patologia , Humanos , Deficiência Intelectual/patologia , Microcefalia/patologia , Fenótipo , Síndrome de Prader-Willi/patologia , Receptor IGF Tipo 1/genética , Adulto JovemRESUMO
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