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262 Comparative investigation of haplotypes in a cohort of unrelated healthy volunteers and Omani CF patients
S118
Posters / Journal of Cystic Fibrosis 15 (2016) S51–S120
Correlations were found between FEV1 , BMI and CFRD. A steeper decline of FEV1 was found in patients with PI and fungi colonization. The 6MWT was performed by 62% of the patients. Correlations were found between desaturation and lower FEV1 , higher Residual Volume and increased number of PEX. Correlations were also identified between walked distance and fungi colonization, PaO2 at rest and PEx. Conclusion: PI and fungi colonization were the major markers of disease severity, characterized by a steeper decline in FEV1 . Desaturation in the 6MWT is linked to a higher number of PEx and fungi colonization also seems to be correlated with a more significant compromise in exercise capacity.
Results: Individual haplotype reconstruction by PHASE® resulted in 18 patterns for healthy individuals and 4 patterns for CF patients. The haplotypes 1–1-1–7-2–1 and 1–1-2–7-2–1 occurred in 55.8% of volunteers. Only the mutations c.274–2A>G and c.1733–1734delTA were within these two major haplotype patterns. In contrast, S549R, DF508 and V392G had the haplotype 2–2-1–6-1–1 which was present in only 2.2% of alleles of healthy individuals. Conclusion: The association of c.274–2A>G and c.1733–1734delTA with the major haplotypes suggests a possible origin of these mutations within the country. In contrast, distant migration of the gene to the country might explain the association of S549R, DF508 and V392G with rare haplotype patterns.
261 Clinical-genetic polymorphism of patients from the National Registry of cystic fibrosis from Republic of Moldova
263 Comparison of FEV1 and BMI of the 4 common CF mutations in UAE
S. Sciuca1 , L. Balanetchi1 , O. Dimitrova1 , C. Grigore1 . 1 State Medical and Pharmaceutical University, Chisinau, Moldova, Republic of
K.Y. Al Redha1 , E. Shebani1 , A. Al Nuaimi1 , J. Panickar1 . 1 Sheikh Khalifa Medical City, Department of Paediatric Respiratory Medicine, Abu Dhabi, United Arab Emirates
Objectives: Rating CFTR mutation spectrum in relation to clinical syndromes in patients with cystic fibrosis, according to the National Registry of CF from Republic of Moldova. Methods: National Register of CF patients in Moldova takes part in the European CF Registry from 2009. Currently the diagnosis of CF in Moldova corresponds to international standards. Results: Over the past seven years the number of CF patients in the National Registry ranges from 41 patients (2009) to 61 patients (2015). The number of adult CF patients is increasing from 14.6% to 21.3%, the maximum age is 37 years. The average age of CF patients, increasing from 8 years to 12 years and age of diagnosis is 2.3–2.9 years without neonatal screening. CFTR gene mutations identified 36.67% homozygous F508del patients, 40% heterozygous F508del and 23.33% with non-F508del genotype. The frequency of other CFTR mutations: 218insA 4 patients; 2789+5G->A, G542X 3 patients each; 1898+1G->A, 3849+10kbC->T, 4015delAC, CFTRdele2,3, W1282X 2 patients each, 10 other rare mutations for one CF patient. Respiratory impairment is present in all CF patients, the most serious pulmonary syndromes were identified in patients of school age and adults with CF. P. aeruginosa lung infections affect up to 60% of CF patients. Episodically detected MRSA, B. cepacia, St. maltophilia. 6.5% of CF patients present a normal pancreatic exocrine function. Index of death is 1–3 CF patients per year. Conclusion: In the Republic of Moldova the National Register of CF patients provides extensive information about CF epidemiology, characteristic of clinical syndromes and genetic spectrum of CFTR mutations.
Background: Paediatric Cystic Fibrosis (CF) centre at SKMC hospital Abu Dhabi, the largest tertiary hospital in United Arab Emirates (UAE), provides tertiary care for all and primary care for majority of CF children in UAE. CF mutations seen in UAE are different to the common CF mutations seen in the western world. We performed a retrospective review, comparing the lung function (FEV1) and BMI of the 4 common CF mutations in UAE. Results: S549R, F508, 1548 del G and 3120+1G>A were the 4 most common mutations seen in our CF population. Mean FEV1 and BMI Z-score of 26 CF children, who carried these mutations, were analysed. For S549R mutations, FEV1 and BMI before and one year after starting ivacaftor were analysed. FEV1 was assessed only for children with good reliable technique. Table: FEV1 and BMI for the 4 most common mutations in UAE CF population Genotype
Mean FEV1
Mean BMI Z-score
S549R/S549R (n = 12) (Pre-ivacaftor) (1 year post-ivacaftor) F508/F508 (n = 8) 1548 del G/1548 del G (n = 3) 3120+1G>A/3120+1G>A (n = 3)
70% 80% 58% 28% 71%
−0.89 −0.55 −1.54 −1.62 −0.08
262 Comparative investigation of haplotypes in a cohort of unrelated healthy volunteers and Omani CF patients
Conclusion: Even though our numbers are not large enough to establish a clear trend, children with S549R and 3120+1G>A mutations had better lung function and BMI compared to children with F508 and 1548 del G mutations. In children with S549R mutations, one year after starting Ivacaftor, a significant improvement of FEV1 and BMI were noted.
M.S. Al Ruhaili1 , T.A. Al Moqbali1 , A.K. Al Kindi1 , M. Al Salmani2 , G. Shivalingam3 , U.W. Fass1 . 1 Oman Medical College, Biochemistry/ Genetics, Sohar, Oman; 2 University Bristol, School of Physiology, Pharmacology and Neuroscience, Bristol, United Kingdom; 3 Sohar Regional Hospital, Paediatrics, Sohar, Oman
264 Natural history of patients with cystic fibrosis carrying nonsense mutations: an analysis of placebo-treated patients from the 009 study
Objectives: The epidemiology of cystic fibrosis (CF) in Oman is different from the rest of the world, with DF508 and S549R affecting 14% and 75% of CF patients, respectively. Other identified CF mutations include c.1733–1734delTA, V392G and c.274–2A>G. To study the genetic makeup of CF transmembrane conductance regulator (CFTR) in Oman, we assessed the distribution of six genetic polymorphisms (KM19MP6d9-J44-GATT-M470V-T845T) in healthy and CF individuals. Method: We used DNA from 32 CF patients and 205 healthy volunteers to amplify the polymorphic sites by PCR. We assessed dimorphic loci by restriction digest and nucleotide repeats by DNA shift assays. We identified diplotypes by allele counting and established haplotypes by three approaches: 1. Allele counting and identifying all unambiguous diplotype phases, 2. Reconstruction of individual haplotypes and 3. Population projected computational iteration of haplotypes by PHASE® software.
E. Kerem1 , I. Sermet-Gaudelus2 , L. Hjelte3 , K. De Boeck4 . 1 Hadassahopital Necker Hebrew University Medical Center, Jerusalem, Israel; 2 Hˆ Enfants Malades, Paris, France; 3 Stockholm CF Center, Stockholm, Sweden; 4 University Hospital Gasthuisberg, Leuven, Belgium Introduction: Patients with nonsense mutation cystic fibrosis (nmCF) are characterized by the absence of functional CFTR protein, associated with a very severe phenotype. Little is currently known about the natural history of nmCF. Aim: To describe the natural history of nmCF by analysing 48-week data on disease parameters in nmCF patients in the placebo arm of a recent phase 3 study that assessed the efficacy and safety of ataluren in patients with nmCF. Methods: Data on lung function parameters, including decline in FEV1 from baseline to 48 weeks, from 116 nmCF patients in the placebo arm of the study were analysed and compared with published data on the overall CF population.
Posters / Journal of Cystic Fibrosis 15 (2016) S51–S120
Correlations were found between FEV1 , BMI and CFRD. A steeper decline of FEV1 was found in patients with PI and fungi colonization. The 6MWT was performed by 62% of the patients. Correlations were found between desaturation and lower FEV1 , higher Residual Volume and increased number of PEX. Correlations were also identified between walked distance and fungi colonization, PaO2 at rest and PEx. Conclusion: PI and fungi colonization were the major markers of disease severity, characterized by a steeper decline in FEV1 . Desaturation in the 6MWT is linked to a higher number of PEx and fungi colonization also seems to be correlated with a more significant compromise in exercise capacity.
Results: Individual haplotype reconstruction by PHASE® resulted in 18 patterns for healthy individuals and 4 patterns for CF patients. The haplotypes 1–1-1–7-2–1 and 1–1-2–7-2–1 occurred in 55.8% of volunteers. Only the mutations c.274–2A>G and c.1733–1734delTA were within these two major haplotype patterns. In contrast, S549R, DF508 and V392G had the haplotype 2–2-1–6-1–1 which was present in only 2.2% of alleles of healthy individuals. Conclusion: The association of c.274–2A>G and c.1733–1734delTA with the major haplotypes suggests a possible origin of these mutations within the country. In contrast, distant migration of the gene to the country might explain the association of S549R, DF508 and V392G with rare haplotype patterns.
261 Clinical-genetic polymorphism of patients from the National Registry of cystic fibrosis from Republic of Moldova
263 Comparison of FEV1 and BMI of the 4 common CF mutations in UAE
S. Sciuca1 , L. Balanetchi1 , O. Dimitrova1 , C. Grigore1 . 1 State Medical and Pharmaceutical University, Chisinau, Moldova, Republic of
K.Y. Al Redha1 , E. Shebani1 , A. Al Nuaimi1 , J. Panickar1 . 1 Sheikh Khalifa Medical City, Department of Paediatric Respiratory Medicine, Abu Dhabi, United Arab Emirates
Objectives: Rating CFTR mutation spectrum in relation to clinical syndromes in patients with cystic fibrosis, according to the National Registry of CF from Republic of Moldova. Methods: National Register of CF patients in Moldova takes part in the European CF Registry from 2009. Currently the diagnosis of CF in Moldova corresponds to international standards. Results: Over the past seven years the number of CF patients in the National Registry ranges from 41 patients (2009) to 61 patients (2015). The number of adult CF patients is increasing from 14.6% to 21.3%, the maximum age is 37 years. The average age of CF patients, increasing from 8 years to 12 years and age of diagnosis is 2.3–2.9 years without neonatal screening. CFTR gene mutations identified 36.67% homozygous F508del patients, 40% heterozygous F508del and 23.33% with non-F508del genotype. The frequency of other CFTR mutations: 218insA 4 patients; 2789+5G->A, G542X 3 patients each; 1898+1G->A, 3849+10kbC->T, 4015delAC, CFTRdele2,3, W1282X 2 patients each, 10 other rare mutations for one CF patient. Respiratory impairment is present in all CF patients, the most serious pulmonary syndromes were identified in patients of school age and adults with CF. P. aeruginosa lung infections affect up to 60% of CF patients. Episodically detected MRSA, B. cepacia, St. maltophilia. 6.5% of CF patients present a normal pancreatic exocrine function. Index of death is 1–3 CF patients per year. Conclusion: In the Republic of Moldova the National Register of CF patients provides extensive information about CF epidemiology, characteristic of clinical syndromes and genetic spectrum of CFTR mutations.
Background: Paediatric Cystic Fibrosis (CF) centre at SKMC hospital Abu Dhabi, the largest tertiary hospital in United Arab Emirates (UAE), provides tertiary care for all and primary care for majority of CF children in UAE. CF mutations seen in UAE are different to the common CF mutations seen in the western world. We performed a retrospective review, comparing the lung function (FEV1) and BMI of the 4 common CF mutations in UAE. Results: S549R, F508, 1548 del G and 3120+1G>A were the 4 most common mutations seen in our CF population. Mean FEV1 and BMI Z-score of 26 CF children, who carried these mutations, were analysed. For S549R mutations, FEV1 and BMI before and one year after starting ivacaftor were analysed. FEV1 was assessed only for children with good reliable technique. Table: FEV1 and BMI for the 4 most common mutations in UAE CF population Genotype
Mean FEV1
Mean BMI Z-score
S549R/S549R (n = 12) (Pre-ivacaftor) (1 year post-ivacaftor) F508/F508 (n = 8) 1548 del G/1548 del G (n = 3) 3120+1G>A/3120+1G>A (n = 3)
70% 80% 58% 28% 71%
−0.89 −0.55 −1.54 −1.62 −0.08
262 Comparative investigation of haplotypes in a cohort of unrelated healthy volunteers and Omani CF patients
Conclusion: Even though our numbers are not large enough to establish a clear trend, children with S549R and 3120+1G>A mutations had better lung function and BMI compared to children with F508 and 1548 del G mutations. In children with S549R mutations, one year after starting Ivacaftor, a significant improvement of FEV1 and BMI were noted.
M.S. Al Ruhaili1 , T.A. Al Moqbali1 , A.K. Al Kindi1 , M. Al Salmani2 , G. Shivalingam3 , U.W. Fass1 . 1 Oman Medical College, Biochemistry/ Genetics, Sohar, Oman; 2 University Bristol, School of Physiology, Pharmacology and Neuroscience, Bristol, United Kingdom; 3 Sohar Regional Hospital, Paediatrics, Sohar, Oman
264 Natural history of patients with cystic fibrosis carrying nonsense mutations: an analysis of placebo-treated patients from the 009 study
Objectives: The epidemiology of cystic fibrosis (CF) in Oman is different from the rest of the world, with DF508 and S549R affecting 14% and 75% of CF patients, respectively. Other identified CF mutations include c.1733–1734delTA, V392G and c.274–2A>G. To study the genetic makeup of CF transmembrane conductance regulator (CFTR) in Oman, we assessed the distribution of six genetic polymorphisms (KM19MP6d9-J44-GATT-M470V-T845T) in healthy and CF individuals. Method: We used DNA from 32 CF patients and 205 healthy volunteers to amplify the polymorphic sites by PCR. We assessed dimorphic loci by restriction digest and nucleotide repeats by DNA shift assays. We identified diplotypes by allele counting and established haplotypes by three approaches: 1. Allele counting and identifying all unambiguous diplotype phases, 2. Reconstruction of individual haplotypes and 3. Population projected computational iteration of haplotypes by PHASE® software.
E. Kerem1 , I. Sermet-Gaudelus2 , L. Hjelte3 , K. De Boeck4 . 1 Hadassahopital Necker Hebrew University Medical Center, Jerusalem, Israel; 2 Hˆ Enfants Malades, Paris, France; 3 Stockholm CF Center, Stockholm, Sweden; 4 University Hospital Gasthuisberg, Leuven, Belgium Introduction: Patients with nonsense mutation cystic fibrosis (nmCF) are characterized by the absence of functional CFTR protein, associated with a very severe phenotype. Little is currently known about the natural history of nmCF. Aim: To describe the natural history of nmCF by analysing 48-week data on disease parameters in nmCF patients in the placebo arm of a recent phase 3 study that assessed the efficacy and safety of ataluren in patients with nmCF. Methods: Data on lung function parameters, including decline in FEV1 from baseline to 48 weeks, from 116 nmCF patients in the placebo arm of the study were analysed and compared with published data on the overall CF population.