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The role of COL19A1 in the pathogenesis of esophageal achalasia
Abstracts / Digestive and Liver Disease 40 (2008) A41–A118
compared to age matched controls with stable chronic liver disease. Material and methods. 29 OLT patients with a mean age of 11.7 ± 3.9 years (range 6–18) have been enrolled for this study. Mean age at the time of OLT was 3.2 ± 3.5 years (range 0.7–9.8). The mean time elapsed since transplantation was 5.1 ± 4.5 years (range 0.7–15.8). The main indications to OLT was Biliary Atresia (90%). Patients have been compared with an age matched control group (CTRL) affected by stable chronic liver disease. All children were regularly attending school. No patient or family was or had been involved in longterm or intensive psychosocial support programs during any phase of the transplantation process. The assessment included individual sessions and testing procedures as follows: 1. CBCL (Child Behaviour Checklist) for assessing behaviour problems and competences of children aged 4–18 years; 2. TMA (Test Multidimensionale dell’Autostima) which is the Italian version of the MSCS (Multidimensional SelfConcept Scale). The TMA assesses self-concept in each of the following six subdomains: Social, Competence, Affect, Academic, Family and Physical. Results. 1. CBCL test. Total Problems Scale showed a statistically significant higher percentage of results within the pathological range in the OLT group (52%) vs CTRL group (17%) (p = 0.03 at exact Fisher Test, EFT). Total Competence Scale showed results within the pathological range in both groups (88% and 92% in OLT and CTRL groups, respectively) with no statistically significant difference (p = 0.67 EFT). 2. TMA. With regard to Self-Concept there were no statistically significant differences between the two groups concerning Social, Competence, Affect, Family and Physical subdomains. Only in the Academic subdomain there was a statistically significant difference in the percentage of patients showing a lower self-concept (50% and 9% in OLT and CTRL groups, respectively) (p = 0.025, EFT). Conclusion. CBCL results confirm that OLT patients have an higher risk for behavioural and emotional disorders as compared to general and hepatopatic peers. OLT and hepatopatic patients difficulties in the social adjustment need further investigation by evaluating also quality of life. Concerning TMA, low scores which have been found in the academic scale underline the existence of activity school lower performances in OLT patients who may therefore require a special support. doi:10.1016/j.dld.2008.07.199
A57
PP15 THE ROLE OF COL19A1 IN THE PATHOGENESIS OF ESOPHAGEAL ACHALASIA E. Piccolo a , G. Gargiulo b , C. Strisciuglio a , A. Del Mastro a , E. Corazziari c , R. Auricchio a a Dipartimento di Pediatria, Università “Federico II”, Naples, Italy b Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy c Dipartimento di Scienze Cliniche, Università “La Sapienza”, Rome, Italy
Aim. Recently it was demonstrated that collagen 19 is expressed in the basal membranes of muscle tissue of oesophagus, expectally in the gastroesophageal junction. Furthermore knock-out mice for COL19A1 gene develop clinical signs of esophageal achalasia (EA), such as megaoesophagous and manometric alteration typical of EA. Materials and methods. 45 patients affected by sporadic EA and 1 patient with a familiar form EA were enrolled in our study. In all patients we performed genomic DNA extraction from peripheral blood, according to standard protocols, and then we screened COL19A1gene by PCR amplification and sequencing of coding regions and joints of intron-exon of the gene. Results. We found two mutations in two different patients and five polymorphisms. The first mutation, in the exon 10, is an heterozygosis G→C, which causes the sostitution of a glycine with a proline (A320P) in a repeated domain of the protein. The second mutation is a deletion of three nucleotides in the exon 32, that causes loss of a glutamine residue in position 712 (del712G) of the protein. Both mutations were not found in 400 healthy chromosomes. Segregation analysis of the two mutations is still in progress. Conclusion. These results demonstrate a possible role of the gene COL19A1 in the pathogenesis of oesophageal achalasia, but to confirm this hypothesis is still necessary to increase the number of patients screenated and analyzes the effects of these mutations in vivo. doi:10.1016/j.dld.2008.07.200 PP16 EARLY VERSUS LATE IMMUNOMODULATORY THERAPY IN PAEDIATRIC CROHN’S DISEASE: A PROSPECTIVE OBSERVATIONAL STUDY IN A TERTIARY REFERRAL CENTRE M. Aloi, O. Iacono, F. Conte, N. Cavallari, F. Viola, F. Nuti, A. Tricarico, L. Fusco, O. Borrelli, S. Cucchiara Pediatric Gastroenterology and Hepatology Unit, La Sapienza University of Rome, Italy Background. Crohn’s disease (CD) is a chronic, relapsing inflammatory disorder of the gut characterized by immune dysregulation, with as many as 25% of patients being
compared to age matched controls with stable chronic liver disease. Material and methods. 29 OLT patients with a mean age of 11.7 ± 3.9 years (range 6–18) have been enrolled for this study. Mean age at the time of OLT was 3.2 ± 3.5 years (range 0.7–9.8). The mean time elapsed since transplantation was 5.1 ± 4.5 years (range 0.7–15.8). The main indications to OLT was Biliary Atresia (90%). Patients have been compared with an age matched control group (CTRL) affected by stable chronic liver disease. All children were regularly attending school. No patient or family was or had been involved in longterm or intensive psychosocial support programs during any phase of the transplantation process. The assessment included individual sessions and testing procedures as follows: 1. CBCL (Child Behaviour Checklist) for assessing behaviour problems and competences of children aged 4–18 years; 2. TMA (Test Multidimensionale dell’Autostima) which is the Italian version of the MSCS (Multidimensional SelfConcept Scale). The TMA assesses self-concept in each of the following six subdomains: Social, Competence, Affect, Academic, Family and Physical. Results. 1. CBCL test. Total Problems Scale showed a statistically significant higher percentage of results within the pathological range in the OLT group (52%) vs CTRL group (17%) (p = 0.03 at exact Fisher Test, EFT). Total Competence Scale showed results within the pathological range in both groups (88% and 92% in OLT and CTRL groups, respectively) with no statistically significant difference (p = 0.67 EFT). 2. TMA. With regard to Self-Concept there were no statistically significant differences between the two groups concerning Social, Competence, Affect, Family and Physical subdomains. Only in the Academic subdomain there was a statistically significant difference in the percentage of patients showing a lower self-concept (50% and 9% in OLT and CTRL groups, respectively) (p = 0.025, EFT). Conclusion. CBCL results confirm that OLT patients have an higher risk for behavioural and emotional disorders as compared to general and hepatopatic peers. OLT and hepatopatic patients difficulties in the social adjustment need further investigation by evaluating also quality of life. Concerning TMA, low scores which have been found in the academic scale underline the existence of activity school lower performances in OLT patients who may therefore require a special support. doi:10.1016/j.dld.2008.07.199
A57
PP15 THE ROLE OF COL19A1 IN THE PATHOGENESIS OF ESOPHAGEAL ACHALASIA E. Piccolo a , G. Gargiulo b , C. Strisciuglio a , A. Del Mastro a , E. Corazziari c , R. Auricchio a a Dipartimento di Pediatria, Università “Federico II”, Naples, Italy b Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy c Dipartimento di Scienze Cliniche, Università “La Sapienza”, Rome, Italy
Aim. Recently it was demonstrated that collagen 19 is expressed in the basal membranes of muscle tissue of oesophagus, expectally in the gastroesophageal junction. Furthermore knock-out mice for COL19A1 gene develop clinical signs of esophageal achalasia (EA), such as megaoesophagous and manometric alteration typical of EA. Materials and methods. 45 patients affected by sporadic EA and 1 patient with a familiar form EA were enrolled in our study. In all patients we performed genomic DNA extraction from peripheral blood, according to standard protocols, and then we screened COL19A1gene by PCR amplification and sequencing of coding regions and joints of intron-exon of the gene. Results. We found two mutations in two different patients and five polymorphisms. The first mutation, in the exon 10, is an heterozygosis G→C, which causes the sostitution of a glycine with a proline (A320P) in a repeated domain of the protein. The second mutation is a deletion of three nucleotides in the exon 32, that causes loss of a glutamine residue in position 712 (del712G) of the protein. Both mutations were not found in 400 healthy chromosomes. Segregation analysis of the two mutations is still in progress. Conclusion. These results demonstrate a possible role of the gene COL19A1 in the pathogenesis of oesophageal achalasia, but to confirm this hypothesis is still necessary to increase the number of patients screenated and analyzes the effects of these mutations in vivo. doi:10.1016/j.dld.2008.07.200 PP16 EARLY VERSUS LATE IMMUNOMODULATORY THERAPY IN PAEDIATRIC CROHN’S DISEASE: A PROSPECTIVE OBSERVATIONAL STUDY IN A TERTIARY REFERRAL CENTRE M. Aloi, O. Iacono, F. Conte, N. Cavallari, F. Viola, F. Nuti, A. Tricarico, L. Fusco, O. Borrelli, S. Cucchiara Pediatric Gastroenterology and Hepatology Unit, La Sapienza University of Rome, Italy Background. Crohn’s disease (CD) is a chronic, relapsing inflammatory disorder of the gut characterized by immune dysregulation, with as many as 25% of patients being