Trend in incidence of gastric adenocarcinoma by tumor location from 1969–2004: a study in one referral center in Iran

AIM: In recent years several studies have shown increasing rate of upper gastric cancers regarding to decrease in distal gastric cancers. The aim of this study was to describe the trend of gastric cancers by location in Iran, which is one of the countries with high prevalence of gastric cancers. METHODS: All registered cases of gasterectomy in Tehran Cancer Institute from 1969 through 2004 were re-evaluated clinicopathologically. The stomach was anatomically divided into the upper, middle, and lower third. The prevalence of gastric cancers in 5 year periods estimated by location and the changes trough the time was evaluated independently and in aspect of age and sex. RESULTS: Over 36 years, the prevalence of cancers in the upper and middle third of the stomach have increased and that of the lower third has decreased. These changes were seen in both sexes and age groups under and over 50 and it was more significant in younger. CONCLUSION: The results are the same as most previous reports in other countries. This can indicate different risk factors as well as confrontation with them. However in regard to few numbers of cases in this study, a population-based study is recommended for confirmation

Epstein-Barr virus associated gastric carcinoma: a report from Iran in the last four decades

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Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu-Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre- or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease-causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.We are indebted to all families for participating in this study. We would like to acknowledge Dr. Natasha Laidlew, who initially suggested the diagnosis in one of the cases and provided important phenotypic information, and Dr. María-Luisa Martínez-Fernández for the critical management of biosamples in ECEMC Program of Spain. Financial assistance was received in support of the study by grants from the German Federal Ministry of Education and Research (BMBF) (GeNeRARe, FKZ: 01GM1519D) to M. Z. and from the Institute of Health Carlos III: Convenio ISCIII-ASEREMAC, and Fundación 1000 sobre Defectos Congénitos, of Spain to E. B.-S. and I. R. G.S

Static telepathology in cancer institute of Tehran university: report of the first academic experience in Iran

<p>Abstract</p> <p>Telepathology is the practice of pathology, which allows quick and timely access to an expert opinion at a distance. We analyzed our new experience in cancer Institute of Tehran University of Medical Sciences with the iPath telepathology server of Basel University. One hundred sixty one cases in a period of 32 months were consulted. These cases received for second evaluation but the definite diagnosis could not be made in this centre. The number of images per case ranged from 3 to 32 (mean: 8). Except one case all cases were evaluated by consultants. Definite final diagnosis was achieved in 88/160 (54.7%). Recommendations for further evaluation were offered in 42/160 cases (26%). Major discrepancies were encountered in 30/160 cases (19%). Thirty-nine of the cases (24.3%) were reported within 1 day. The rate of achieving final diagnosis was higher in histological group rather than cytological ones. Increase in number of H&E images had no significant effect on achieving a definite final diagnosis. The rate of achieving final diagnosis in this study is much lower than other similar studies, which could be due to inappropriate sampling images, a potential cause of misdiagnosis in static telepathology. The other possible reason is that all of the cases in this study were problematic cases that a definite diagnosis could not be made for them even in primary consultation. The mean time for achieving a final diagnosis was also more than other studies, which could be for the reasons mentioned above.</p

5p13 microduplication in a malformed fetus and his unaffected father

The 5p13 microduplication syndrome is a contiguous gene syndrome characterized by developmental delay intellectual disability, hypotonia, unusual facies with marked variability, mild limb anomalies, and in some cases brain malformations. The duplication ranges in size from 0.25 to 1.08 Mb and encompasses five genes (NIPBL, SLC1A3, CPLANE1, NUP155, and WDR70), of which NIPBL has been suggested to be the main dose sensitive gene. All patients with duplication of the complete NIPBL gene reported thus far have been de novo. Here, we report a 25-week-old male fetus with hypertelorism, wide and depressed nasal bridge, depressed nasal tip, low-set ears, clenched hands, flexion contracture of elbows, knees, and left wrist, and bilateral clubfeet, bowing and shortening of long bones and brain malformation of dorsal part of callosal body. The fetus had a 667 kb gain at 5p13.2 encompassing SLC1A3, NIPBL and exons 22–52 of CPLANE1. The microduplication was inherited from the healthy father, in whom no indication for mosaicism was detected. The family demonstrates that incomplete penetrance of 5p13 microduplication syndrome may occur which is important in genetic counseling of families with this entity

Widespread aplasia cutis congenita in sibs with PLEC1 and ITGB4 variants

Aplasia cutis congenita (ACC) is a heterogeneous group of disorders characterized by localized or widespread absence of skin. ACC can occur isolated or as part of a syndrome. Here we report two consanguineous families, each with two affected offspring. Affected individuals showed widespread ACC while the skin in between had a normal appearance. Ears and nose of the four patients were underdeveloped, otherwise there were no unusual physical characteristics and no internal organ anomalies. “Whole” exome sequencing (WES) of the mother of Family 1 yielded a pathogenic heterozygote variant in ITGB4. The father and healthy offspring were heterozygous for the same variant. WES of the mother of Family 2 yielded a variant in PLEC1. The father and grandmother, who had a history of two offspring with fatal ACC, were heterozygous for the same variant. PLEC1 and ITGB4 have both been previously been reported in association with ACC. We compare findings in earlier reported individuals with variants in ITGB4 and PLEC1, and provide a short summary of other entities going along with ACC

Mutations in GRIP1 Cause Fraser Syndrome

Background: Fraser syndrome (FS) is a autosomal recessive malformation syndrome characterised by cryptophthalmos, syndactyly and urogenital defects. FS is a genetically heterogeneous condition. Thus far, mutations in FRAS1 and FREM2 have been identified as cause of FS. Both FRAS1 and FREM2 encode extracellular matrix proteins that are essential for the adhesion between epidermal basement membrane and the underlying dermal connective tissues during embryonic development. Mutations in murine Grip1, which encodes a scaffolding protein that interacts with Fras1/Frem proteins, result in FS-like defects in mice. Objective: To test GRIP1 for genetic variants in FS families that do not have mutations in FRAS1 and FREM2. Methods and results: In three unrelated families with parental consanguinity, GRIP1 mutations were found to segregate with the disease in an autosomal recessive manner (donor splice site mutation NM_021150.3:c.2113+1G→C in two families and a 4-bp deletion, NM_021150.3:c.1181_1184del in the third). RT-PCR analysis of the GRIP1 mRNA showed that the c.2113+1G→C splice mutation causes skipping of exon 17, leading to a frame shift and a premature stop of translation. Conclusion: Mutations in GRIP1 cause classic FS in humans

Mutations in GRIP1 cause Fraser syndrome

Background Fraser syndrome (FS) is a autosomal recessive malformation syndrome characterised by cryptophthalmos, syndactyly and urogenital defects. FS is a genetically heterogeneous condition. Thus far, mutations in FRAS1 and FREM2 have been identified as cause of FS. Both FRAS1 and FREM2 encode extracellular matrix proteins that are essential for the adhesion between epidermal basement membrane and the underlying dermal connective tissues during embryonic development. Mutations in murine Grip1, which encodes a scaffolding protein that interacts with Fras1/Frem proteins, result in FS-like defects in mice. Objective To test GRIP1 for genetic variants in FS families that do not have mutations in FRAS1 and FREM2. Methods and results In three unrelated families with parental consanguinity, GRIP1 mutations were found to segregate with the disease in an autosomal recessive manner (donor splice site mutation NM_021150.3: c.2113+1G -> C in two families and a 4-bp deletion, NM_021150.3: c.1181_1184del in the third). RT-PCR analysis of the GRIP1 mRNA showed that the c.2113+1G -> C splice mutation causes skipping of exon 17, leading to a frame shift and a premature stop of translation. Conclusion Mutations in GRIP1 cause classic FS in human