| 1. |
- Bergman, Annika, et al.
(författare)
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Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer
- 2009
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Taylor & Francis. - 0284-4311 .- 1651-2073. ; 43:5, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- Saethre-Chotzen syndrome is one of the most common craniosynostosis syndromes. It is an autosomal dominantly inherited disorder with variable expression that is caused by germline mutations in the TWIST1 gene or more rarely in the FGFR2 or FGFR3 genes. We have previously reported that patients with Saethre-Chotzen syndrome have an increased risk of developing breast cancer. Here we have analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to study whether a proportion of these families might have mutations in Saethre-Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic mutations in the coding sequence in any of the 26 patients. MLPA (multiplex ligation-dependent probe amplification)-analysis also showed no alterations in copy numbers in any of the craniofacial disorder genes MSX2, ALX4, RUNX2, EFNB1, TWIST1, FGFR1, FGFR2,FGFR3, or FGFR4. Taken together, our findings indicate that mutations in Saethre-Chotzen-associated genes are uncommon or absent in BRCA1/2-negative patients with hereditary breast cancer.
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| 2. |
- Lidberg, Ulf, 1962, et al.
(författare)
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Genomic organization, sequence analysis, and chromosomal localization of the human carboxyl ester lipase (CEL) gene and a CEL-like (CELL) gene.
- 1992
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Ingår i: Genomics. - 0888-7543. ; 13:3, s. 630-40
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Tidskriftsartikel (refereegranskat)abstract
- The gene encoding human carboxyl ester lipase (CEL), including 1628 bp of the 5'-flanking region, has been isolated and characterized from two overlapping lambda phage clones. The gene spans 9832 bp and contains 11 exons interrupted by 10 introns. The exons range in size from 88 to 204 bp, except for the last exon, which is 841 bp. A major and a minor transcription initiation site were determined 13 and 7 bp, respectively, upstream of the initiator methionine. The nucleotide sequence is identical with that of the previously reported cDNA, except for the third nucleotide in the 5'-untranslated sequence, a C, which in the cDNA is a T. A TAAATA sequence is present 26 nt upstream from the major CAP site, and within the 5'-flanking region there are several putative transcription factor binding sites. Seven Alu repetitive sequence elements are present in the region analyzed. The organization of the human CEL gene is similar to that of the recently reported rat pancreatic cholesterol esterase gene. The CEL gene was assigned to chromosome 9q34-qter, which confirms the recently reported results of Tayler et al. (1991, Genomics 10: 425-431). A previously unknown gene with a striking homology to the human CEL gene, here called the CEL-like gene (CELL), has also been isolated and characterized, including 1724 bp of the 5'-flanking region. The CELL gene, which most likely is a psuedogene, spans 4846 bp, and due to the absence of a 4.8-kb segment, the CEL gene exons 2-7 are not present in the CELL gene. Despite these differences, the CELL gene is transcribed. We have also assigned the CELL gene to a separate locus at chromosome 9q34-qter.
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| 3. |
- Rüetschi, Ulla, 1962, et al.
(författare)
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Human 4-hydroxyphenylpyruvate dioxygenase. Primary structure and chromosomal localization of the gene.
- 1993
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Ingår i: European journal of biochemistry / FEBS. - 0014-2956. ; 213:3, s. 1081-9
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Tidskriftsartikel (refereegranskat)abstract
- We report the primary structure of 4-hydroxyphenylpyruvate dioxygenase [4-hydroxyphenyl-pyruvate:oxygen oxidoreductase (hydroxylating, decarboxylating)]. The work is based on the isolation of cDNA clones from human liver lambda gt11 libraries. Several overlapping clones covering the coding sequence were characterized. In parallel, peptides from four different digests of the purified protein were analysed for their amino-acid sequence. These peptide sequences covered 86% of the cDNA-derived amino-acid sequence. This gives the sequence for a polypeptide of 392 amino acids with a calculated molecular mass of 44.8 kDa. There is more than 80% identity between the human and the pig enzymes and also between these enzymes and the F antigen from rat and the two allelic forms of this antigen from mouse. The enzyme has 53% conserved amino acids and 27% identical amino acids in common with 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. P.J. 874 and 52% conserved and 28% identical residues, with a protein from Shewanella colwelliana. At the C-terminus there is 61% identity between the seven proteins. These results indicate that these proteins are all 4-hydroxyphenylpyruvate dioxygenases. The identity of the C-terminus makes this part of the molecule a candidate for a functional role in the catalytic process. At conserved positions in all seven enzymes, there are two tyrosine residues and three histidine residues, i.e. amino acids which have been implicated as ligands for iron in 2-oxoacid-dependent dioxygenases. The gene encoding the enzyme was localized to chromosome 12q14-->qter by Southern-blot analysis of human-rodent somatic-cell hybrids.
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| 4. |
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| 5. |
- Sahlin, Pelle, et al.
(författare)
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Women with Saethre-Chotzen syndrome are at increased risk of breast cancer.
- 2007
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:7, s. 656-60
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Tidskriftsartikel (refereegranskat)abstract
- The Saethre-Chotzen syndrome is an autosomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1. This syndrome has hitherto not been associated with an increased risk of cancer. However, recent studies, using a murine breast tumor model, have shown that Twist may act as a key regulator of metastasis and that the gene is overexpressed in subsets of sporadic human breast cancers. Here, we report a novel association between the Saethre-Chotzen syndrome and breast cancer. In 15 Swedish Saethre-Chotzen families, 15 of 29 (52%) women carriers over the age of 25 had developed breast cancer. At least four patients developed breast cancer before 40 years of age, and five between 40 and 50 years of age. The observed cases with breast cancer (n = 15) are significantly higher than expected (n = 0.89), which gives a standardized incidence ratio (SIR) of 16.80 (95% CI 1.54-32.06). Our finding of a high frequency of breast cancer in women with the Saethre-Chotzen syndrome identifies breast cancer as an important and previously unrecognized symptom characteristic of this syndrome. The results strongly suggest that women carriers of this syndrome would benefit from genetic counseling and enrolment in surveillance programs including yearly mammography. Our results also indicate that the TWIST1 gene may be a novel breast cancer susceptibility gene. Additional studies are, however, necessary to reveal the mechanism by which TWIST1 may predispose to early onset breast cancer in Saethre-Chotzen patients.
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| 6. |
- Windh, Per, et al.
(författare)
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Spring-assisted cranioplasty vs pi-plasty for sagittal synostosis--a long term follow-up study.
- 2008
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Ingår i: The Journal of craniofacial surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1049-2275. ; 19:1, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- Spring-assisted cranioplasty (SAS) has been used for the treatment of selected cases of sagittal synostosis at our unit routinely since 1998. In order to assess the long-term outcomes of this procedure, we compared the clinical data and morbidity with the pi-plasty technique, our previous standard procedure for the treatment of such children.The first 20 consecutive patients who underwent SAS for isolated sagittal synostosis with complete records, and who were 3 years old at the time of this study, were included. Twenty patients with a pi-plasty performed in the period immediately preceding the spring group acted as a control group. Cephalograms (preoperative, 1-year and 3-year), clinical examination, medical record data, medical photography, and a questionnaire (spring-group only) were used to evaluate and compare these two groups.The mean age of the spring group was 3.5 months (2.5-5.5) and the pi-plasty group 7.1 months (4-15.5) of age at surgery. There were no deaths in either group. There was a higher rate of complications in the pi-plasty group. The skull morphology was similar preoperatively in both groups but slightly different at the 3-year follow-up. The mean cephalic index (CI) in the spring group was 72 at 1 year of age and 71 at 3 years of age, indicating a minor relapse. The pi-plasty group had a mean CI of 73 at 3 years of age. The length was the same in both groups however the pi-plasty group had a lower height (mean 2 mm) and wider biparietal distance (mean 5 mm). All parents of the spring group were highly satisfied with the aesthetic results achieved, would undergo the operation again, and would recommend it to others with scaphocephaly.It was concluded that the two groups of surgery resulted in a quite similar morphologic outcome. The pi-plasty group had a cephalic index marginally closer to the normal range at 3 years of age. The spring group was superior with respect to blood loss, transfusion requirements, operative time, ICU time, recovery time, and total hospital stay.
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