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Article: Proportion of cystic fibrosis gene mutations not detected by routine testing in men with obstructive azoospermia

TitleProportion of cystic fibrosis gene mutations not detected by routine testing in men with obstructive azoospermia
Authors
Issue Date1999
PublisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtl
Citation
Journal Of The American Medical Association, 1999, v. 281 n. 23, p. 2217-2224 How to Cite?
AbstractContext: Infertile men with obstructive azoospermia may have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of which are rare in classic cystic fibrosis and not evaluated in most routine mutation screening. Objective: To assess how often CFTR mutations or sequence alterations undetected by routine screening are detected with more extensive screening in obstructive azoospermia. Design: Routine screening for the 31 most common CFTR mutations associated with the CF phenotype in white populations, testing for the 5-thymidine variant of the polythymidine tract of intron 8 (IVS8-5T) by allele-specific oligonucleotide hybridization, and screening of all exons through multiplex heteroduplex shift analysis followed by direct DNA sequencing. Setting: Male infertility clinic of a Canadian university-affiliated hospital. Subjects: Of 198 men with obstructive (n = 149) or nonobstructive (n = 49; control group) azoospermia, 64 had congenital bilateral absence of the vas deferens (CBAVD), 10 had congenital unilateral absence of the vas deferens (CUAVD), and 75 had epididymal obstruction (56/75 were idiopathic). Main Outcome Measure: Frequency of mutations found by routine and nonroutine tests in men with obstructive vs nonobstructive azoospermia. Results: Frequency of mutations and the IVS8-ST variant in the nonobstructive azoospermia group (controls) (2% and 5.1% allele frequency, respectively) did not differ significantly from that in the general population (2% and 5.2%, respectively). In the CBAVD group, 72 mutations were found by DNA sequencing and IVS8-ST testing (47 and 25, respectively; P < .001 and P = .002 vs controls) vs 39 by the routine panel (P < .001 vs controls). In the idiopathic epididymal obstruction group, 24 mutations were found by DNA sequencing and IVS8-5T testing (12 each; P = .01 and P = .14 vs controls) vs 5 by the routine panel (P = .33 vs controls). In the CUAVD group, 2 mutations were found by routine testing (P = .07 vs controls) vs 4 (2 each, respectively; P = .07 and P = .40 vs controls) by DNA sequencing and IVS8-ST testing. The routine panel did not identify 33 (46%) of 72.2 (50%) of 4, and 19 (79%) of 24 detectable CFTR mutations and IVS8-ST in the CBAVD, CUAVD, and idiopathic epididymal obstruction groups, respectively. Conclusions: Routine testing for CFTR mutations may miss mild or rare gene alterations. The barrier to conception for men with obstructive infertility has been overcome by assisted re productive technologies, thus raising the concern of iatrogenically transmitting pathogenic CFTR mutations to the progeny.
Persistent Identifierhttp://hdl.handle.net/10722/44353
ISSN
2015 Impact Factor: 37.684
2015 SCImago Journal Rankings: 6.440
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMak, Men_HK
dc.contributor.authorZielenski, Jen_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorDurie, Pen_HK
dc.contributor.authorZini, Aen_HK
dc.contributor.authorMartin, Sen_HK
dc.contributor.authorLongley, TBen_HK
dc.contributor.authorJarvi, KAen_HK
dc.date.accessioned2007-09-12T03:51:58Z-
dc.date.available2007-09-12T03:51:58Z-
dc.date.issued1999en_HK
dc.identifier.citationJournal Of The American Medical Association, 1999, v. 281 n. 23, p. 2217-2224en_HK
dc.identifier.issn0098-7484en_HK
dc.identifier.urihttp://hdl.handle.net/10722/44353-
dc.description.abstractContext: Infertile men with obstructive azoospermia may have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of which are rare in classic cystic fibrosis and not evaluated in most routine mutation screening. Objective: To assess how often CFTR mutations or sequence alterations undetected by routine screening are detected with more extensive screening in obstructive azoospermia. Design: Routine screening for the 31 most common CFTR mutations associated with the CF phenotype in white populations, testing for the 5-thymidine variant of the polythymidine tract of intron 8 (IVS8-5T) by allele-specific oligonucleotide hybridization, and screening of all exons through multiplex heteroduplex shift analysis followed by direct DNA sequencing. Setting: Male infertility clinic of a Canadian university-affiliated hospital. Subjects: Of 198 men with obstructive (n = 149) or nonobstructive (n = 49; control group) azoospermia, 64 had congenital bilateral absence of the vas deferens (CBAVD), 10 had congenital unilateral absence of the vas deferens (CUAVD), and 75 had epididymal obstruction (56/75 were idiopathic). Main Outcome Measure: Frequency of mutations found by routine and nonroutine tests in men with obstructive vs nonobstructive azoospermia. Results: Frequency of mutations and the IVS8-ST variant in the nonobstructive azoospermia group (controls) (2% and 5.1% allele frequency, respectively) did not differ significantly from that in the general population (2% and 5.2%, respectively). In the CBAVD group, 72 mutations were found by DNA sequencing and IVS8-ST testing (47 and 25, respectively; P < .001 and P = .002 vs controls) vs 39 by the routine panel (P < .001 vs controls). In the idiopathic epididymal obstruction group, 24 mutations were found by DNA sequencing and IVS8-5T testing (12 each; P = .01 and P = .14 vs controls) vs 5 by the routine panel (P = .33 vs controls). In the CUAVD group, 2 mutations were found by routine testing (P = .07 vs controls) vs 4 (2 each, respectively; P = .07 and P = .40 vs controls) by DNA sequencing and IVS8-ST testing. The routine panel did not identify 33 (46%) of 72.2 (50%) of 4, and 19 (79%) of 24 detectable CFTR mutations and IVS8-ST in the CBAVD, CUAVD, and idiopathic epididymal obstruction groups, respectively. Conclusions: Routine testing for CFTR mutations may miss mild or rare gene alterations. The barrier to conception for men with obstructive infertility has been overcome by assisted re productive technologies, thus raising the concern of iatrogenically transmitting pathogenic CFTR mutations to the progeny.en_HK
dc.languageengen_HK
dc.publisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtlen_HK
dc.relation.ispartofJournal of the American Medical Associationen_HK
dc.titleProportion of cystic fibrosis gene mutations not detected by routine testing in men with obstructive azoospermiaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0098-7484&volume=281&issue=23&spage=2217&epage=2224&date=1999&atitle=Proportion+of+cystic+fibrosis+gene+mutations+not+detected+by+routine+testing+in+men+with+obstructive+azoospermiaen_HK
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturelink_to_OA_fulltexten_HK
dc.identifier.doi10.1001/jama.281.23.2217en_HK
dc.identifier.pmid10376575-
dc.identifier.scopuseid_2-s2.0-0033575077en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033575077&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume281en_HK
dc.identifier.issue23en_HK
dc.identifier.spage2217en_HK
dc.identifier.epage2224en_HK
dc.identifier.isiWOS:000080777000036-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMak, M=7003466815en_HK
dc.identifier.scopusauthoridZielenski, J=7003732699en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridDurie, P=7005360997en_HK
dc.identifier.scopusauthoridZini, A=7005212511en_HK
dc.identifier.scopusauthoridMartin, S=35611051800en_HK
dc.identifier.scopusauthoridLongley, TB=6603428591en_HK
dc.identifier.scopusauthoridJarvi, KA=23392788300en_HK

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