RESUMO
We report on a girl with Giuffrè-Tsukahara syndrome manifesting microcephaly, mental retardation, radio-ulnar synostosis, short stature and scoliosis. Skewed X-inactivation was not observed in our patient. We reviewed previous reports and provide evidence in support of X-linked dominant inheritance of this condition.
Assuntos
Doenças Genéticas Ligadas ao Cromossomo X/genética , Transtornos do Crescimento/genética , Microcefalia/genética , Escoliose/genética , Sinostose/genética , Feminino , Genes Dominantes , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Transtornos do Crescimento/patologia , Humanos , Recém-Nascido , Microcefalia/patologia , Escoliose/patologia , Síndrome , Sinostose/patologiaRESUMO
OBJECTIVE: Present study deals with LOH and MSI in FHIT gene and p53 expression in GBC, CC, XGC, and normal GB to elucidate the role of FHIT gene in gall bladder cancer. METHODS: Five microsatellite markers D3S1217, D3S1300, D3S1313, D3S1600, and D3S2757, were selected. RESULTS: Among GBC cases the frequency of MSI-H and LOH was 17.5% and 27.5%, respectively. Significant difference was found between GBC and normal GB (p = .02), and GBC and CC groups (p= .002) when LOH was compared. CONCLUSIONS: Our results suggested CC might act as a preinvasive stage in the pathogenesis of GBC.
Assuntos
Hidrolases Anidrido Ácido/genética , Colecistite/genética , Doenças da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/genética , Instabilidade Genômica , Proteínas de Neoplasias/genética , Proteína Supressora de Tumor p53/genética , Xantomatose/genética , Hidrolases Anidrido Ácido/fisiologia , Adulto , Idoso , Colecistite/metabolismo , Colecistite/patologia , Doença Crônica , DNA/sangue , DNA/genética , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Progressão da Doença , Feminino , Doenças da Vesícula Biliar/metabolismo , Doenças da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Humanos , Perda de Heterozigosidade , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/fisiologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Proteína Supressora de Tumor p53/biossíntese , Xantomatose/metabolismo , Xantomatose/patologiaRESUMO
Bone marrow aspiration is the preliminary investigation in Niemann Pick disease type A when enzyme assays and mutation studies are unavailable. We report an infant with typical phenotype and enzyme deficiency, but undetectable Niemann Pick cells in the bone marrow. A new mutation R542X in SMPD gene was also detected.
Assuntos
Células da Medula Óssea/patologia , Doença de Niemann-Pick Tipo A/diagnóstico , Análise Mutacional de DNA , Humanos , Lactente , Masculino , Mutação , Doença de Niemann-Pick Tipo A/genética , Doença de Niemann-Pick Tipo A/patologia , Esfingomielina Fosfodiesterase/genéticaRESUMO
The aim was to investigate the genomic instability in the E-cadherin (CDH1) gene and to correlate it with its protein expression in gall bladder cancer (GBC) and in other gall bladder (GB) diseases viz. chronic cholecystitis (CC), xantho-granulomatous cholecystitis (XGC), and normal GB to explicate its role in GBC tumorigenesis. Microsatellite instability (MSI) and loss of heterozygosity (LOH) in CDH1 were studied using D16S421, D16S496, D16S503, D16S512, D16S2624, and D16S3021 microsatellite markers and D2S123 (2p16), D2S382 (2q24), D6S292 (6q21-23), D7S480 (7q31), and D17S796 (17p13.1-3) were used to investigate genomic instability at 2p, 2q, 6q, 7q, and 17p loci in 40 GBC, 50 CC, 34 XGC, and 15 normal GB cases. Immunohistochemistry was carried out to analyze the E-cadherin and p53 protein expression. Overall LOH in CDH1 and other markers was high in GBC and XGC as compared to CC; however, it did not correlate with its protein expression in GBC cases. Loss of E-cadherin expression was high in GBC (67%), while majority of the CC (94%) and XGC (91%) cases retained positive E-cadherin expression. Overexpression of p53 was high in GBC (43%) whereas CC, XGC, normal GB cases were negative for p53 overexpression. None of the normal GB cases showed genomic instability at any of the markers. High LOH in CDH1 and other chromosomal loci in GBC indicated that the genomic instability followed a GBC>XGC>CC trend during the process of neoplastic transformation in GB, highlighting the fact that CC might act as a precursor lesion of GBC.