RESUMO
Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia in the neonatal and early infancy periods. Althought the disease is relatively rare with incidence of about 1:25 000-50 000 live births, the importance of the disease should not be underestimated. Namely, prompt recognition and management of patients with CHI is essential, if permanent neurological impairment is to be avoided. CHI is caused by mutations in one of the 7 genes involved in the regulation of insulin secretion in pancreatic beta-cells. It is important to introduce specific medical therapy as soon as diagnosis is established. Severe, neonatal forms of CHI are often resistant to medications, thus they require surgical procedure. The preoperative genetic testing and scintigraphy are indicated to distinguish histological subtypes of the disease (focal vs. diffuse CHI). Patients with focal disease are usually cured after pancreatic resection, while diffuse disease has much worse prognosis. This manuscript offers novel insights into CHI and emphasizes the role of early diagnosis as crucial for succesful treatment that was recently enriched with novel options.
Assuntos
Hiperinsulinismo Congênito , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/terapia , Humanos , Recém-NascidoRESUMO
AIM: To determine the value of short-tandem repeat markers on the chromosome X (X-STR) for prenatal diagnostics of the chromosome X numerical disorders. METHODS: We investigated the genetic variability of 5 X-markers (DXS9895, DXS6810, DXS6803, GATA172D05, and HPRTB) in 183 healthy Croatian individuals (90 men and 93 women). We also tested 13 patients with X chromosome disorders (Turner syndrome--6 cases; Klinefelter syndrome--5 cases, and Triple X syndrome--2 cases). The analysis was performed using polymerase chain reaction amplification with specific primers and electrophoresis on a polyacrylamide gel. The study was performed in 2010. RESULTS: Our sample showed no significant differences in allelic frequencies of the investigated X-markers from other European populations. A set of 5 X-STR markers was sufficiently informative for a successful determination of the chromosome X numerical abnormalities. CONCLUSION: Since no false positive or negative results were observed, diagnostic value of the investigated X-STR loci for prenatal detection of chromosome X numerical disorders was confirmed. Our study represents an important step toward an improved prenatal diagnostics in Croatia.
Assuntos
Genes Ligados ao Cromossomo X/genética , Repetições de Microssatélites/genética , Diagnóstico Pré-Natal , Transtornos dos Cromossomos Sexuais/genética , Sequência de Bases/genética , Distribuição de Qui-Quadrado , Croácia , Feminino , Amplificação de Genes , Humanos , Masculino , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Transtornos dos Cromossomos Sexuais/diagnóstico , Fatores de TempoRESUMO
Pallister Killian syndrome (PKS) is a rare genetic disorder caused by tetrasomy of the short arm of chromosome 12, revealed usually in mosaic distribution of an extra i (12) (p10) chromosome in fibroblasts. The syndrome presents with a recognizable pattern of findings including pigmentary skin changes, coarse face, high forehead, sparse anterior scalp hair, hypertelorism, seizures and progressive psychomotor developmental delay. It was first described independently by Pallister in 1977 and by Killian and Teschler-Nikola in 1981. We report a case of 21 month old girl with PKS and significant overgrowth. Cytogenetic analysis was performed using the GTG banding technique. The karyotype of cultured lymphocytes was normal. The karyotype from skin fibroblasts was established as mosaic tetrasomy of 12p 47,XX,+i (12) (p10)/46,XX. The origin of the extra marker chromosome was determinated by fluorescence in situ hybridization with chromosome 12 specific DNA probes confirming that supernumerary marker is chromosome i (12p) in 68% of cells. Despite the excessive postnatal growth we found low serum growth hormone levels and reduced response to pharmacological stimulation test. This is also the first report of a postnatal patient in our country.
Assuntos
Anormalidades Múltiplas/patologia , Aberrações Cromossômicas , Deficiências do Desenvolvimento/patologia , Transtornos do Crescimento/patologia , Transtornos da Pigmentação/patologia , Anormalidades Múltiplas/genética , Cromossomos Humanos Par 12 , Deficiências do Desenvolvimento/genética , Feminino , Fibroblastos/patologia , Marcadores Genéticos , Transtornos do Crescimento/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Linfócitos/patologia , Transtornos da Pigmentação/genéticaRESUMO
Great studies of multiple myeloma (MM) strongly suggested that specific chromosomal changes are of prognostic significance in patients with MM1. We have performed cytogenetic analysis and recently fluorescent in situ hybridization (FISH) on 43 cases of MM. Clonal chromosomal changes were present in 24 (56%) cases. Hyperdiploid karyotype was found in 12 (50%) cases, hypodiploid in 8 (33%) cases, and 4 (17%) cases had a pseudodiploid karyotype. The most common numerical abnormalities were gains of whole chromosomes 15, 11, 3 and 6. Whole chromosome losses were also frequent involving chromosomes X, 13, 14, and 8. Most cases showed also structural rearrangements 71% (n = 17): del(1p), dup(1q), del(5q), del(13q), del(17p) and t(11;14)(q13;q32) (n = 4, 17%). Chromosome -13/13q deletion was found in 42% (n = 10) cases; complete loss of 13 was observed in 67% (n = 7) cases, whereas 33% (n = 3) had interstitial deletions. In the majority of the cases there was a mixture of abnormal and normal metaphases.
Assuntos
Aberrações Cromossômicas , Bandeamento Cromossômico , Hibridização in Situ Fluorescente , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Biópsia por Agulha , Medula Óssea/patologia , Deleção Cromossômica , Feminino , Rearranjo Gênico , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Translocação GenéticaRESUMO
Hypophosphatasia is a metabolic bone disease characterized by bone and teeth hypomineralization due to defective function of tissue-nonspecific alkaline phosphatase (TNSALP). The disorder is caused by various mutations in the TNSALP gene localized on short arm of chromosome 1. Infantile hypophosphatasia is a severe form of the disease inherited as an autosomal recessive trait which presents before age of six months and often has fatal outcome. We report a patient with typical clinical course for infantile hypophosphatasia who was homozygous for the c.1402G>A mutation. The same mutation has been previously associated with a more severe perinatal form also in a Croatian family what indicates a possible common ancestral origin and phenotypic variability potential of c.1402G>A mutation of TNSALP gene.
Assuntos
Fosfatase Alcalina/genética , Hipofosfatasia/genética , Mutação de Sentido Incorreto , Fosfatase Alcalina/deficiência , Croácia , Evolução Fatal , Feminino , Humanos , Hipofosfatasia/diagnóstico por imagem , Recém-Nascido , RadiografiaRESUMO
In this study we reported the results for the first time of applying Polymerase Chain Reaction-Short Tandem Repeats (PCR-STR) method in the field of detection of aneuploidies for chromosomes 21 and 18 in Croatians. The aims of the study were: (I) validation of the diagnostic informativeness of 6 STR loci (D18S51, D18S858, D18S535, D21S1435, D21S1411, and D21S1414) in sample of 205 unrelated healthy individuals; (II) evaluation of diagnostic power of the PCR-STR method for those 6 microsatellites; (III) establishment protocol for use STRs as routine method for rapid prenatal detection of trisomy 21 and 18. DNA samples were amplified by fluorescence-based PCR reaction, subjected to electrophoresis in automated laser fluorescence DNA sequencer (ALFexpress). Results of our study were: (I) all 6 tested loci are informative (68-85% of heterozygous individuals); (II) comparison between PCR-STR method and conventional cytogenetics did not revealed any false positive or false negative results; (III) in prenatal screening of 105 samples of uncultured amniotic fluid 6 (5.7%) samples with chromosomal abnormalities were identified.
Assuntos
Amniocentese , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/métodos , Cromossomos Humanos Par 18 , Síndrome de Down/diagnóstico , Repetições de Microssatélites/genética , Trissomia/diagnóstico , Adulto , Croácia , Método Duplo-Cego , Feminino , Triagem de Portadores Genéticos , Humanos , Gravidez , Sensibilidade e EspecificidadeRESUMO
A 17-year-old Croatian boy with Nijmegen breakage syndrome (NBS) who developed diffuse large B-cell non-Hodgkin lymphoma is presented. The majority of the patients with this rare autosomal recessive disease are of Slavic origin and, in most of them, the disease is caused by NBS1 mutation 657del5, as was found in our patient. Nijmegen breakage syndrome is characterized by microcephaly, growth retardation, abnormal facial appearance, spontaneous chromosomal rearrangements, immunodeficiency, and a high predisposition to cancer development, predominantly lymphoma. Because of increased sensitivity to radiation therapy and chemotherapy, the treatment of malignancies in patients with NBS can be difficult. To our knowledge, our patient is the first with NBS reported in the literature who was successfully treated for diffuse large B-cell lymphoma with the anti-CD20 monoclonal antibody rituximab in addition to a modified dose of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy. He has been in complete remission for 3 years after finishing the treatment.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/complicações , Linfoma de Células B/tratamento farmacológico , Síndrome de Quebra de Nijmegen/complicações , Adolescente , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Humanos , Cariotipagem , Masculino , Síndrome de Quebra de Nijmegen/genética , Prednisona/administração & dosagem , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Conventional cytogenetics detected an interstitial deletion of proximal region of p-arm of chromosome 2 in a 6-month-old boy with a phenotype slightly resembling Down's syndrome. The deletion was inherited from the father, whose karyotype revealed a small ring-shaped marker chromosome, in addition to interstitial deletion. Fluorescence in situ hybridization identified the marker, which consisted of the proximal region of the p-arm of chromosome 2, including a part of its centromere. This case shows that molecular cytogenetic analysis can reveal the mechanism of the formation of the marker chromosome.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 2/ultraestrutura , Cromossomos em Anel , Análise Citogenética , Marcadores Genéticos/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino , Sensibilidade e EspecificidadeRESUMO
Glutaric aciduria type 1 (GA 1) is a preventable cause of acute brain damage in early childhood, leading to a severe dystonic-dyskinetic disorder. Typically between 6 and 18 months of age, a non-specific illness such as respiratory or gastrointestinal infection or immunization leads to encephalopathic crisis, usually resulting in degeneration of the putamen and caudate. GA 1 is an autosomal recessive disease of catabolism of amino acids lysine, hydroxylysine and tryptophane leading to accumulation of glutaric acid, 3-hydroxyglutaric acid and glutaconic acid. Recognition of this biochemical disorder before the brain has been injured is essential to the outcome. Diagnosis depends upon the recognition of relatively non-specific physical findings such as hypotonia, tremor, irritability and macrocephaly, and on urinary organic acids analysis. The diagnosis may also be suggested by characteristic findings of neuroimaging. Specific management includes pharmacological doses of 1-carnitine and dietary protein restriction. Metabolic decompensation must be treated vigorously to avoid permanent brain damage. With this case report the authors want to contribute to the early recognition of GA1, to the prevention of the related brain damage, and to increase awareness of the existence of so-called cerebral organic acidurias.