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Microphthalmia is not a mandatory finding in X-linked recessive syndromic microphthalmia caused by the recurrent BCOR variant p.Pro85Leu.
Kraus, C, Uebe, S, Thiel, CT, Ekici, AB, Reis, A, Zweier, C
American journal of medical genetics. Part A. 2018;(12):2872-2876
Abstract
Mutations in BCOR cause X-linked dominant and X-linked recessive forms of syndromic microphthalmia. By exome sequencing, we identified the recurrent BCOR mutation p.Pro85Leu in two brothers and their unaffected mother. While the older brother's phenotype completely fits the described phenotypic spectrum of X-linked recessive BCOR-associated Lenz microphthalmia syndrome, the younger brother showed developmental delay, microcephaly, and skeletal anomalies, but not the key feature of microphthalmia. In contrast to the previously published families, our findings demonstrate a large variability of BCOR-associated, syndromic phenotypes, indicating incomplete penetrance of p.Pro85Leu with regards to microphthalmia in males.
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De novo exon 1 missense mutations of SKI and Shprintzen-Goldberg syndrome: two new cases and a clinical review.
Au, PY, Racher, HE, Graham, JM, Kramer, N, Lowry, RB, Parboosingh, JS, Innes, AM, ,
American journal of medical genetics. Part A. 2014;(3):676-84
Abstract
Shprintzen-Goldberg syndrome (OMIM #182212) is a connective tissue disorder characterized by craniosynostosis, distinctive craniofacial features, skeletal abnormalities, marfanoid body habitus, aortic dilatation, and intellectual disability. Mutations in exon 1 of SKI have recently been identified as being responsible for approximately 90% of reported individuals diagnosed clinically with Shprintzen-Goldberg syndrome. SKI is a known regulator of TGFβ signaling. Therefore, like Marfan syndrome and Loeys-Dietz syndrome, Shprintzen-Goldberg syndrome is likely caused by deregulated TGFβ signals, explaining the considerable phenotypic overlap between these three disorders. We describe two additional patients with exon 1 SKI mutations and review the clinical features and literature of Shprintzen-Goldberg syndrome.
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Multiple mutations in the Kras gene in colorectal cancer: review of the literature with two case reports.
Macedo, MP, Andrade, Lde B, Coudry, R, Crespo, R, Gomes, M, Lisboa, BC, Aguiar, S, Soares, FA, Carraro, DM, Cunha, IW
International journal of colorectal disease. 2011;(10):1241-8
Abstract
PURPOSE Kras mutations are negative predictors of anti-EGFR therapy, occurring in 40% of colorectal carcinomas (CRCs). Point substitutions in codon 12 or 13 are the most frequent mutations in Kras, but multiple mutations (MMs) in other codons can also develop. Few data exist on MMs with regard to their frequency and the codons and amino acids that are affected. We report two cases of Kras double mutations in codons 12 and 13 and review Kras MMs in primary CRC in PubMed databases. CASE REPORT A 53-year-old woman and a 70-year-old man presented with deep, invasive, moderately differentiated CRC at an advanced clinical stage. The former had regional lymph node involvement and vaginal wall neoplastic implantation, and the latter had liver metastasis. Primary tumors were examined for Kras mutations by pyrosequencing, which were confirmed by direct sequencing. Both tumors had a mutation in codons 12 and 13, wherein codon 12 was mutated to GAT, and codon 13 became GAC. CONCLUSIONS We identified 69 reported cases of Kras MMs and reported two other cases, representing 2.1% of all mutated tumors; the incidence of such mutations is 1.0% in CRC patients. In most cases (59%), MMs develop in a single codon, usually codon 12. Codons 12 and 13 are affected simultaneously in only 27% of cases. These findings add information about the impact of specific amino acid changes in the Kras gene.
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A novel K-ras mutation in colorectal cancer. A case report and literature review.
Palmirotta, R, Savonarola, A, Formica, V, Ludovici, G, Del Monte, G, Roselli, M, Guadagni, F
Anticancer research. 2009;(8):3369-74
Abstract
BACKGROUND Activating mutations in the K-ras oncogene mainly occur in codons 12 and 13 and may be predictive of response to drugs directly linked to the K-ras signaling pathway, such as panitumumab and cetuximab. MATERIALS AND METHODS K-ras analysis was carried out on DNA extracted from paraffin-embedded tumor samples after microdissection. Exons 1 and 2 were amplified by PCR and then sequenced. RESULTS A never-reported K-ras mutation (CAG>TAG) determining a premature stop signal at codon 22 (Gln22Stop) was found in a patient with metastatic colorectal cancer. BRAF and p53 were not found to be modified and microsatellite instability was not present. The patient, however, was found to be unresponsive to an anti-EGFR MAb treatment. CONCLUSION This study is the first report of a novel K-ras truncating mutation in a patient with metastatic colorectal cancer and is also suggestive for the evaluation of alternative pathways to better identify individuals who are likely to benefit from targeted therapies.
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Identification of the first patient with a confirmed mutation of the JAK-STAT system.
Rosenfeld, RG, Kofoed, E, Buckway, C, Little, B, Woods, KA, Tsubaki, J, Pratt, KA, Bezrodnik, L, Jasper, H, Tepper, A, et al
Pediatric nephrology (Berlin, Germany). 2005;(3):303-5
Abstract
Growth hormone insensitivity (GHI) has been attributable, classically, to mutations in the gene for the GH receptor. After binding to the GH receptor, GH initiates signal transduction through a number of pathways, including the JAK-STAT pathway. We describe the first patient reported with a mutation in the gene for STAT5b, a protein critical for the transcriptional regulation of insulin-like growth factor-I.