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Conference Paper: CFTR: I1023R is a rare but recurrent disease-causing mutation found in Chinese patients with cystic fibrosis

TitleCFTR: I1023R is a rare but recurrent disease-causing mutation found in Chinese patients with cystic fibrosis
Authors
Issue Date2014
PublisherThe Hong Kong College of Paediatricians.
Citation
The 2nd Annual Scientific Meeting of the Hong Kong College of Paediatricians, Hong Kong, China, 6 December 2014. In Program Book, 2014, p. 18 How to Cite?
AbstractBackground: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene CFTR. CF is a common in Caucasians, yet less than twenty Chinese patients with molecular confirmation have been reported. Our department is the only center that offers sweat test in Hong Kong, and from our data we estimate the incidence of CF as 1 in 300,000 in local Chinese. We report the findings of a comprehensive genetic analysis of 6 unrelated Chinese patients with the clinical suspicion of CF. Methods and results: Using NGS (next generation sequencing), Sanger sequencing and MLPA (multiplex ligationdependent probe amplification), we screened for single nucleotide variations and deletion/ duplications in all exons and three intronic hotspots of CFTR gene. Molecular diagnosis was confirmed in four unrelated patients. Importantly, three inherited the same missense mutation, I1023R (CFTR: NM_000492.3: c.T3068G), which was reported only in two Taiwanese siblings with CF but not in patients of other ethnicities. Patients with this recurrent mutation have typical CF features, including Pseudomonas aeuroginosa pneumonia, bronchiectasis and meconium ileus. It is not found in our in-house database of 200 exomes, or public databases like ESP6500 and 1000GP, indicating a very low allelic frequency. Using linkage and functional analysis, we showed that I1023R is likely a founder mutation in Hans Chinese and the mutant CFTR protein is potentially having a post-translational defect, resulting in reduced expression compared with the wild-type protein. Conclusion: We have summarized the diagnosis of all reported CF patients in the last twenty years. In addition to our genetic analysis of local patients, we propose that I1023R is a rare but recurrent, potential founder type disease-causing CFTR mutation in Chinese CF patients. Currently I1023R is not a screening target in the cystic fibrosis mutation panel (i.e. ACMG25) which includes the core mutations recommended by American College of Medical Genetics (ACMG). This finding has implications in the design of mutation panels, and analysis of NGS for molecular diagnosis of CF for Chinese patients.
DescriptionOutstanding Oral Presentation
Oral Free Paper Session
Persistent Identifierhttp://hdl.handle.net/10722/207354

 

DC FieldValueLanguage
dc.contributor.authorLeung, KCen_US
dc.contributor.authorMak, CCYen_US
dc.contributor.authorChen, YXen_US
dc.contributor.authorChau, CSKen_US
dc.contributor.authorYing, Den_US
dc.contributor.authorChu, WYen_US
dc.contributor.authorLi, AMen_US
dc.contributor.authorYang, Wen_US
dc.contributor.authorLau, YLen_US
dc.contributor.authorChan, KYKen_US
dc.contributor.authorChen, JHen_US
dc.contributor.authorLee, SLen_US
dc.contributor.authorChung, BHYen_US
dc.date.accessioned2014-12-19T11:02:34Z-
dc.date.available2014-12-19T11:02:34Z-
dc.date.issued2014en_US
dc.identifier.citationThe 2nd Annual Scientific Meeting of the Hong Kong College of Paediatricians, Hong Kong, China, 6 December 2014. In Program Book, 2014, p. 18en_US
dc.identifier.urihttp://hdl.handle.net/10722/207354-
dc.descriptionOutstanding Oral Presentation-
dc.descriptionOral Free Paper Session-
dc.description.abstractBackground: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene CFTR. CF is a common in Caucasians, yet less than twenty Chinese patients with molecular confirmation have been reported. Our department is the only center that offers sweat test in Hong Kong, and from our data we estimate the incidence of CF as 1 in 300,000 in local Chinese. We report the findings of a comprehensive genetic analysis of 6 unrelated Chinese patients with the clinical suspicion of CF. Methods and results: Using NGS (next generation sequencing), Sanger sequencing and MLPA (multiplex ligationdependent probe amplification), we screened for single nucleotide variations and deletion/ duplications in all exons and three intronic hotspots of CFTR gene. Molecular diagnosis was confirmed in four unrelated patients. Importantly, three inherited the same missense mutation, I1023R (CFTR: NM_000492.3: c.T3068G), which was reported only in two Taiwanese siblings with CF but not in patients of other ethnicities. Patients with this recurrent mutation have typical CF features, including Pseudomonas aeuroginosa pneumonia, bronchiectasis and meconium ileus. It is not found in our in-house database of 200 exomes, or public databases like ESP6500 and 1000GP, indicating a very low allelic frequency. Using linkage and functional analysis, we showed that I1023R is likely a founder mutation in Hans Chinese and the mutant CFTR protein is potentially having a post-translational defect, resulting in reduced expression compared with the wild-type protein. Conclusion: We have summarized the diagnosis of all reported CF patients in the last twenty years. In addition to our genetic analysis of local patients, we propose that I1023R is a rare but recurrent, potential founder type disease-causing CFTR mutation in Chinese CF patients. Currently I1023R is not a screening target in the cystic fibrosis mutation panel (i.e. ACMG25) which includes the core mutations recommended by American College of Medical Genetics (ACMG). This finding has implications in the design of mutation panels, and analysis of NGS for molecular diagnosis of CF for Chinese patients.-
dc.languageengen_US
dc.publisherThe Hong Kong College of Paediatricians.-
dc.relation.ispartofAnnual Scientific Meeting of the Hong Kong College of Paediatriciansen_US
dc.titleCFTR: I1023R is a rare but recurrent disease-causing mutation found in Chinese patients with cystic fibrosisen_US
dc.typeConference_Paperen_US
dc.identifier.emailChau, CSK: skchau@hku.hken_US
dc.identifier.emailYing, D: jonson@hku.hken_US
dc.identifier.emailChu, WY: chuwyy@hku.hken_US
dc.identifier.emailYang, W: yangwl@hkucc.hku.hken_US
dc.identifier.emailLau, YL: lauylung@hku.hken_US
dc.identifier.emailLee, SL: slleem@hku.hken_US
dc.identifier.emailChung, BHY: bhychung@hku.hken_US
dc.identifier.authorityYang, W=rp00524en_US
dc.identifier.authorityLau, YL=rp00361en_US
dc.identifier.authorityChung, BHY=rp00473en_US
dc.identifier.hkuros241863en_US
dc.identifier.spage18-
dc.identifier.epage18-
dc.publisher.placeHong Kong-

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