RESUMO
Germline DNA alterations affecting homologous recombination pathway genes have been associated with pancreatic cancer (PC) risk. BRCA2 is the most studied gene and affects the management of PC patients and their families. Even though recent reports have suggested a similar role of germline ATM pathogenic variants (PV) in familial PC, there is still a disagreement between experts on how it could affect patient management given the lack of proper PC risk estimates. We retrospectively analyzed the germline data of 257 PC patients among whom nearly 50% were sporadic cases. We showed similar frequencies of BRCA2 (4.9%) and ATM (4.4%) PV or likely pathogenic variants, which were not related to familial history. Based on our findings and that of the literature, we suggest including ATM gene among the panel of genes analyzed in PC patients pending the publication of prospective studies.
Assuntos
Predisposição Genética para Doença , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Mutação em Linhagem Germinativa , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologiaAssuntos
Carcinoma de Células Escamosas , Doenças da Unha , Neoplasias Uveais , Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Células Germinativas , Mutação em Linhagem Germinativa , Humanos , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genéticaRESUMO
BACKGROUND: Klinefelter syndrome (KS), a common sex chromosome aneuploidy (47,XXY) is diagnosed prenatally with an incidence of 0.15%. The diagnosis is generally incidental, since there are no typical malformations on ultrasound (US). Once detected, genetic counseling is often difficult and the parents' decision to continue or terminate the pregnancy is greatly dependent on the amount and nature of the information provided. We sought to assess the pregnancy outcomes (i.e. continuation versus termination) and the influence of multidisciplinary centers for prenatal diagnosis on parental decisions in cases of KS. METHODS: From 1985 to 2009, 188 prenatal diagnoses of KS were made by 11 participating laboratories in mainland France. In each case, the karyotype indication, parental ages, year of prenatal testing, sampling procedure, karyotype, associated US findings and outcome were recorded. RESULTS AND CONCLUSIONS: The pregnancy termination rate declined markedly over time, from 46.9% before 1997 to 11.6% thereafter, in line with the introduction of new legislation on prenatal diagnosis for medical reasons and, more specifically, the creation of multidisciplinary prenatal diagnosis centers. However, an additional microdeletion in one KS infant who exhibited echogenic bowel on US was unfortunately diagnosed postnatally. This raises the question as to whether array comparative genomic hybridization should be prenatally advised when US abnormalities are detected, in line with advice for fetuses with a normal karyotype.
Assuntos
Aborto Induzido/estatística & dados numéricos , Síndrome de Klinefelter/diagnóstico , Diagnóstico Pré-Natal , Revelação , Feminino , França , Aconselhamento Genético , Humanos , Cariótipo , Síndrome de Klinefelter/epidemiologia , Síndrome de Klinefelter/genética , Masculino , Gravidez , Resultado da GravidezRESUMO
The inherited disorders of CNS myelin formation represent a heterogeneous group of leukodystrophies. The proteolipoprotein (PLP1) gene has been implicated in two X-linked forms, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2, and the gap junction protein alpha12 (GJA12) gene in a recessive form of PMD. The myelin basic protein (MBP) gene, which encodes the second most abundant CNS myelin protein after PLP1, presents rearrangements in hypomyelinating murine mutants and is always included in the minimal region deleted in 18q- patients with an abnormal hypomyelination pattern on cerebral MRI. In this study, we looked at the genomic copy number at the Golli-MBP locus in 195 patients with cerebral MRI suggesting a myelin defect, who do not have PLP1 mutation. Although preliminary results obtained by FISH suggested the duplication of Golli-MBP in 3 out of 10 patients, no abnormal gene quantification was found using Quantitative Multiplex PCR of Short Fluorescent fragments (QMPSF), Multiplex Amplifiable Probe Hybridization (MAPH), or another FISH protocol using directly-labelled probes. Pitfalls and interest in these different techniques to detect duplication events are emphasised. Finally, the study of this large cohort of patients suggests that Golli-MBP deletion or duplication is rarely involved in inherited defects of myelin formation.
Assuntos
Dosagem de Genes/genética , Proteínas do Tecido Nervoso/genética , Paraplegia/genética , Doença de Pelizaeus-Merzbacher/genética , Fatores de Transcrição/genética , Primers do DNA , Sondas de DNA/genética , Duplicação Gênica , Humanos , Hibridização in Situ Fluorescente , Imageamento por Ressonância Magnética , Proteínas de Membrana , Proteína Básica da Mielina , Proteína Proteolipídica de Mielina , Reação em Cadeia da Polimerase/métodosRESUMO
Heterochromatin confined to pericentromeric and secondary constriction regions plays a major role in morphological variation of chromosome 9, because of its size and affinity for pericentric inversion. We report on a 6-year-old boy with growth and language delay, minor facial anomalies and unusual chromosome 9 variant with an extra-band in the centromeric region on the conventional karyotype. Subsequent analysis by FISH and CGH identified this variant as a dicentric chromosome 9 with a duplication of the 9p12-q21 region. An identical chromosome 9 variant was found in the mild language retarded brother and in the phenotypically normal father and grandfather. The presumed mechanism accounting for the phenotypic discordance observed in this family and the usefulness of CGH in characterization of such variants are discussed. To our knowledge, this is the first investigation of an unusual chromosome 9 variant by CGH.
