Genética Médica
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- Schimke immuno-osseous dysplasia: case report and review of 25 patientsPublication . Saraiva, JM; Dinis, A; Resende, C; Faria, E; Gomes, C; Correia, AJ; Gil, J; Fonseca, NImmuno-osseous dysplasia is characterised by spondyloepiphyseal dysplasia, lymphopenia with defective cellular immunity, and progressive renal disease. We describe a patient with a severe form of the disease, review the features of another 24 patients, and discuss the previous classification. The differences between the two groups are not striking, and although similarities are greater between affected sibs, the same diagnosis of Schimke immuno-osseous dysplasia should apply to them all. The aetiology and physiopathology of this rare osteochondrodysplasia of presumed autosomal recessive inheritance remain unknown.
- Analysis of human spermatozoa by fluorescence in situ hybridization with preservation of the head morphology is possible by avoiding a decondensation treatmentPublication . Almeida-Santos, T; Dias, C; Brito, R; Henriques, P; Almeida-Santos, APURPOSE: Development of a hybridization technique for spermatozoa allowing the preservation of the head morphology. METHODS: FISH analysis of fixed semen samples from oligoasthenoteratozoospermia (OAT) patients with a normal somatic karyotype attending the Cytogenetics and the IVF Laboratories of a University hospital for semen analysis. In situ hybridization with centromeric probes for chromosomes X, Y, and 18 and locus specific probe for chromosome 21. RESULTS: More than 95% of the sperm heads showed clear hybridization signals and a conserved morphology including the visualization of the tail. Few cells with splitted signals were not considered. CONCLUSIONS: This is the first description of a simple and fast hybridization protocol for spermatozoa without a decondensation step, allowing preservation of the morphology of the sperm head that is particularly useful to correlate abnormal spermatozoa with specific chromosome aneuploidies. With this technique we were able to avoid troubles in interpretation of FISH spots that does not depend on the quality of nuclear decondensation, as it is the case in the previously described methods. Our goal was to demonstrate the efficiency of the method without loosing sperm head morphology. Further studies are needed to correlate the aneuploidy rates for specific chromosomes with sperm morphology.
- Carcinoma do Endométrio em Mulheres Jovens: caso clínicoPublication . Godinho, I; Sousa, R; Silva, T; Regateiro, FJ; Oliveira, CF; Oliveira, HM
- Cytogenetic analysis of spontaneously activated noninseminated oocytes and parthenogenetically activated failed fertilized human oocytes--implications for the use of primate parthenotes for stem cell productionPublication . Almeida-Santos, T; Dias, C; Henriques, P; Brito, R; Barbosa, A; Regateiro, FJ; Almeida-Santos, APURPOSE:Spontaneous parthenogenetically activated noninseminated oocytes and failed fertilized oocytes after ART activated by puromycin were studied to assess cleavage ability and the cytogenetic constitution of the resulting embryos. METHODS: Failed fertilized oocytes were exposed to puromycin, and whenever activation occurred, they were further cultured until arrest of development. FISH was used to assess the ploidy of spontaneous (group A) and induced parthenotes (group B). RESULTS: The mean number of oocytes exposed to puromycin and the percentage and type of activation were identical in IVF and ICSI patients. The more frequent types of activation were one or two pronuclei and one polar body suggesting that retention of the second polar body is a common event after parthenogenetic activation. CONCLUSIONS: Retention of the second polar body and chromosome malsegregation were observed after parthenogenetic activation, either spontaneous or induced by puromycin. This means that using parthenogenetic embryos for stem cell research will require great care and attention.
- Dual use of Diff-Quik-like stains for the simultaneous evaluation of human sperm morphology and chromatin statusPublication . Sousa, AP; Tavares, RS; Velez de la Calle, JF; Figueiredo, H; Almeida, V; Almeida-Santos, T; Ramalho-Santos, JBACKGROUND: Sperm chromatin status and nuclear DNA damage can be detected using well-established assays. However, most techniques are time-consuming and/or involve elaborate protocols and equipment. We have recently developed a simple and fast method to monitor sperm chromatin status in field conditions using the Diff-Quik assay which is employed in fertility clinics to assess sperm morphology with standard bright field microscopy. In the present study, we demonstrate that any Diff-Quik-like stain can easily, reproducibly and routinely monitor human sperm chromatin status as well. METHODS: Different Diff-Quik-like stains were used to assess sperm morphology and the presence of abnormal dark nuclear staining in human sperm from four ART centres. The TUNEL assay was performed in the same samples, and fertility outcomes were assessed. RESULTS: A significant correlation was found between TUNEL-positive sperm and dark sperm nuclei. Moreover, associations were also found between the percentage of dark sperm nuclei and seminal parameters, embryo development rate, embryo quality and clinical pregnancy, as well as with cryptorchidism, and there was a tendency towards an association with age. A value of 32% abnormal staining is suggested as a predictive threshold for embryo development and pregnancy. CONCLUSIONS: Our results show that any Diff-Quik-like stain, already implemented in most laboratories to assess sperm morphology, can be adapted as an indicator for chromatin status in human sperm.
- Dilated fetal bowel as indication for prenatal diagnosis of cystic fibrosisPublication . Soares, R; Neto, P; Pereira, N; Cunha, C; Pinto, C; Fonseca, M; Ramos, L; Galhano, EDilated fetal bowel is a sonographic fi nding that is associated to meconium ileus, a feature of cystic fi brosis (CF). Prenatal diagnosis of CF is possible through analysis of the cystic fi brosis transmembrane regulator gene mutations. A male infant is described, who was referred to our Prenatal Diagnosis Center a 17th week of gestation with a dilated bowel loop on a prenatal scan. Amniocentesis was performed at 23rd week gestation and a homozygous F508del mutation was found. He was born at 38 weeks gestation, after an otherwise unremarkable pregnancy, and admitted to Neonatal Intensive Care Unit. He showed progressive abdominal distension without stools and was transferred to another Hospital to surgery. A total occlusion of terminal ileum with meconium and a microcolon were found, and resection of 8 cm of ileum and an ileostomy were performed. The characteristic sonographic fi nding of a dilated bowel is an indication to search for CF mutations.
- Hiperplasia congénita da supra-renal: quando o mesmo genótipo tem diferentes fenótiposPublication . Cordinhã, C; Morais, S; Cardoso, R; Ramos, L; Taborda, A; Mirante, A
- Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?Publication . Morimoto, M; Yu, Z; Stenzel, P; Clewing, JM; Najafian, B; Mayfield, C; Hendson, G; Weinkauf, JG; Gormley, AK; Saraiva, JMBACKGROUND: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown. METHODS: We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients. RESULTS: Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression. CONCLUSIONS: This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD.
- Inv21p12q22del21q22 and intellectual disabilityPublication . Oliveira, R; Dória, S; Madureira, C; Lima, V; Almeida, C; Pinho, MJ; Ramalho, C; Matoso, E; Barros, A; Carreira, IM; Moura, CPChromosomal rearrangements are common in humans. Pericentric inversions are among the most frequent aberrations (1-2%). Most inversions are balanced and do not cause problems in carriers unless one of the breakpoints disrupts important functional genes, has near submicroscopic copy number variants or hosts "cryptic" complex chromosomal rearrangements. Pericentric inversions can lead to imbalance in offspring. Less than 3% of Down syndrome patients have duplication as a result of parental pericentric inversion of chromosome 21. We report a family with an apparently balanced pericentric inversion of chromosome 21. The proband, a 23-year-old female was referred for prenatal diagnosis at 16weeks gestation because of increased nuchal translucency. She has a familial history of Down's syndrome and moderate intellectual disability, a personal history of four spontaneous abortions and learning difficulties. Peripheral blood and amniotic fluid samples were collected to perform proband's and fetus' cytogenetic analyses. Additionally, another six family members were evaluated and cytogenetic analysis was performed. Complementary FISH and MLPA studies were carried out. An apparent balanced chromosome 21 pericentric inversion was observed in four family members, two revealed a recombinant chromosome 21 with partial trisomy, and one a full trisomy 21 with an inverted chromosome 21. Array CGH analysis was performed in the mother and the brother's proband. MLPA and aCGH studies identified a deletion of about 1.7Mb on the long arm of inverted chromosome 21q22.11. We believe the cause of the intellectual disability/learning difficulties observed in the members with the inversion is related to this deletion. The recombinant chromosome 21 has a partial trisomy including the DSCR with no deletion. The risk for carriers of having a child with multiple malformations/intellectual disability is about 30% depending on whether and how this rearrangement interferes with meiosis.
- Avaliação e Investigação Etiológica do Atraso do Desenvolvimento Psicomotor / Défice IntelectualPublication . Oliveira, R; Rodrigues, F; Venâncio, M; Saraiva, JM; Fernandes, BDevelopmental Delay (DD) and Intellectual Disability (ID), depending on the affected individual being under or above five years-old, result from environmental or genetic causes during the developmental period, that manifest as a subnormal functioning of intellectual abilities. In western countries there is a prevalence of about 3%, with a great impact in the individuals, their families, as well as in the society. Etiologic diagnosis remains unknown in about 65-80% of the cases. It is a clinically heterogeneous condition as it can be sporadic or familiar, encompassing an autosomal dominant, recessive or X-linked transmission. Etiologic investigation emphasizes the importance of the clinical and family history as well as the physical examination, with special care for dysmorphologic evaluation. The authors reviewed DD/ ID focusing not only on clinical diagnosis but mostly on genetic causes and etiologic investigation. The protocol presented is followed by the Medical Genetics Department of Coimbra’s Paediatrics Hospital, in accordance to the international consensus.
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