Nazneen Rahman

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..Finally, it is probable that the genes underlying a substantial component of susceptibility to breast cancer remain to be identified...

..5). Meiotic recombinants place the gene for JHF within a 7-cM interval bounded by D4S2393 and D4S395...

..Mutational screening of the microfibril-associated glycoprotein-2 gene, a strong candidate within the minimal interval, did not reveal any likely pathogenic mutations...

..005) to carry missense mutations, suggesting that the underlying NSD1 mutational mechanism in Sotos syndrome may influence reproductive fitness...

..i.) = 1.4-3.9, P = 0.0025). The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia-DNA repair pathway and breast cancer predisposition...

..Finally, we identified a locus on chromosome 9 (rs755383, OR=1.37, P=1.12x10(-23)), containing the sex determination gene DMRT1, which has been linked to teratoma susceptibility in mice...

..These findings have important implications for models of disease predisposition and clinical translation...

..Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers...

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..Exome sequencing in common conditions will therefore require intelligent sample and variant prioritisation strategies in large case-control studies to deliver robust genetic evidence of disease association...

..Our data establish EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth...

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..37 (95% confidence interval (c.i.) = 1.51-3.78, P = 0.0003). There was no evidence that other classes of ATM variant confer a risk of breast cancer...

..32 × 10(-14)) and 11q14 (rs790356, P = 4.25 × 10(-15)). Both regions contain genes that are plausibly related to Wilms tumorigenesis. We also identified candidate association signals at 5q14, 22q12 and Xp22...

..001). These data provide new insights into the pattern, order, interactions and clinical associations of molecular events in Wilms tumor...

..These observations raise interesting implications with respect to the identification and phenotypic characterization of cancer predisposition genes...

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..Overall, these data suggest that families with both Wilms tumor and neuroblastoma represent a previously unrecognized familial cancer syndrome in which the underlying predisposition gene(s) remain to be determined...

..This finding strongly suggests that aneuploidy is causally related to cancer development...

..Moreover, we show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers...

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..These data suggest that the genetic progression in rhabdomyosarcoma from MVA and non-MVA cases may be similar, but that somatic BUB1B mutations are unlikely to be common in sporadic childhood cancers known to be associated with MVA...

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..CEP57 is a centrosomal protein and is involved in nucleating and stabilizing microtubules. Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division...

..More recently, the NSD1 mutational spectrum has been defined, the phenotype of Sotos syndrome clarified and diagnostic and management guidelines developed...

..The impact on clinical management dictates that constitutional 11p15 analysis should be considered in all individuals with Wilms tumor...

..These data (1) demonstrate that JHF and ISH are allelic conditions and (2) implicate perturbation of basement-membrane matrix assembly as the cause of the characteristic perivascular hyaline deposition seen in these conditions...

..Constitutional DICER1 mutations were recently reported to cause familial pleuropulmonary blastoma (PPB)...

..These recent advances herald a new chapter in the exploration of susceptibility to breast cancer and are likely to provide insights relevant to other common, heterogeneous diseases...

..These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development...

..The results indicate that FA gene mutations, other than in BRCA2, are unlikely to be a frequent cause of highly penetrant breast cancer predisposition...

..These data identify RNF135 as causative of a new overgrowth syndrome and demonstrate that RNF135 haploinsufficiency contributes to the phenotype of NF1 microdeletion cases...

..05-3.19), P = 10(-31)). KITLG, encoding the ligand for the receptor tyrosine kinase KIT, which has previously been implicated in the pathogenesis of TGCT and the biology of germ cells, may explain the association on chromosome 12...

..A mutation or microdeletion of NSD1 is diagnostic of Sotos syndrome...

..Elucidation of the mechanisms underlying cancer in overgrowth syndromes might yield important insights into the molecular basis of childhood tumors...

..Our results provide important physiological evidence that the first 40 amino acids of WT1 are capable of functionally important interactions, presumably through their ability to self-associate with full-length WT1...

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..We sought to ascertain the frequency and heritability of constitutional WT1 mutations in nonsyndromic WT patients...

..It is important to consider this diagnosis in children presenting with malignancy and abnormal skin pigmentation, even in the absence of a strong family history of tumors...

..We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes...

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..These results indicate that 1100delC may be the only CHEK2 allele that makes an appreciable contribution to breast cancer susceptibility...

..Muscle biopsy revealed myopathic changes, which have not been reported previously. We suggest that skeletal muscle is involved in Infantile Systemic Hyalinosis and contributes to the characteristic poor outcome of these patients...

..Neuroblastoma is a malignant condition of the developing sympathetic nervous system that most commonly affects young children and is often lethal. Its cause is not known...

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..Manifestations in the present family include dramatically increased height, weight, and head circumference together with a long face, large mandible, and large ears, but mental deficiency was absent...

..Altogether, these results suggest RAD50 can only be making a very minor contribution to familial breast cancer predisposition in UK and Finland...

..They also indicate that no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2...

..This provides further evidence that the underlying PHOX2B mutational mechanism influences tumor risk and suggests that the position of missense mutations may influence the resulting phenotype...

..Combined analysis generated a multipoint LOD score of 2.1 at marker D12S1583 and refined the HMSN IIC gene interval to The clinical and molecular findings are discussed...

..Our results suggest that the risk of cancer associated with CHEK2 1100delC mutations is restricted to breast cancer, although we cannot rule out a small increase in overall cancer risk...

..05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach...

..00005, respectively). Further validation may prove this tumor classifier to be useful for selecting familial breast cancer cases for further mutation screening, particularly, as these data can be obtained using archival tissue...

..02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies...

..65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer...

..These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases...

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..This approach enabled the discovery of candidate genes for developmental diseases including autism...

..The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes...

..In this case report, periodontal status, treatment and follow-up together with histopathologic evaluation of gingival tissue specimens and mutation screening of two JHF cases are presented...

..In contrast, recently, another group described mutations in the UMOD gene as responsible for MCKD2 and familial juvenile hyperuricemic nephropathy (FJHN)...