ABCMdb

PMID: 14998948

Danziger KL, Black LD, Keiles SB, Kammesheidt A, Turek PJ
Improved detection of cystic fibrosis mutations in infertility patients with DNA sequence analysis.
Hum Reprod. 2004 Mar;19(3):540-6. Epub 2004 Jan 29., [PubMed]

Sentences

No. Mutations Sentence Comment

59 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ile148Thr ABCC7 p.Gln493* ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Arg560Thr ABCC7 p.Tyr1092* ABCC7 p.Phe508Cys Polyacrylamide gels were analysed for the presence of mutations following staining in ethidium bromide (EtBr) and image capture under UV using the Gel Doc 1000 system Table I. List of CFTR mutations included in common mutation panels American College of Medical Genetics CF panel (25 mutations) DF508 G542X G551D R117H W1282X N1303K R1162X 3849+10kbC®T DI507 R553X 1717-1G®A 621+1G®T R560T 3659delC 3120+1G®A I148T G85E R334W A455E 1898+1G®A 2148delA 711+1G®T 2789+5G®A R347P 1078delT Six additional mutations and one polymorphism in UCSF panel (31 mutations) Y1092X R347H 3849+4 Q493X 3905insT S549N F508C (polymorphism) (BioRad). Login to comment 84 ABCC7 p.Val201Met ABCC7 p.Pro750Leu ABCC7 p.Val520Ile Diagnosis/clinical information Ancestry 5T allele Common mutation panel Sequence method Interpretation Mutation panel/ DNA sequence concordance 1 CBAVD N.E. Cauc. Negative Negative Het. P750L Mutation No 2 CBAVD Asian Het. Negative Negative No mutation detected Yes 3 CBAVD Asian Negative Negative Het. V201M Mutation No 4 CBAVD Asian-Indian Het. Negative Het. 1717±4A®G Variant of unknown signi®cance No 5 CBAVD Asian Negative * V520I/3601±3C®A Mutation/variant of unknown signi®cance Nod 6 CBAVDa N.E./S.E. Login to comment 85 ABCC7 p.Arg117His ABCC7 p.Trp1098Cys ABCC7 p.Ile556Val ABCC7 p.Val456Ala ABCC7 p.Gln1352His ABCC7 p.Ile807Met Cauc. Het. * DF508/R117H Mutation/mutation Yesd 7 CBAVD Asian-Indian Het. Negative Het. V456A Mutationc No 8 CBAVD Asian Negative * Het. Q1352H Mutation Nod 9 CBAVD Asian Negative * Negative No mutation detected Yes 10 CBAVDb N.E. Cauc./ Asian/Ashkenazi Negative * I556V/2752±26A®G Mutation/mutation Nod 11 CBAVD Hispanic Homozygous * Het. W1098C Mutation Nod 12 CBAVD Asian Negative Negative Het. 3499+25C®G Variant of unknown signi®cance No 13 CUAVD Hispanic Negative * Negative No mutation detected Yes 14 CBAVDb N.E. Cauc. Negative * Negative No mutation detected Yes 15 Idiopathic obstruction Asian-Indian Negative * Het. I807M Mutationc Nod 16 Idiopathic obstruction N.E. Cauc. Het. * Het. DF508 Mutation Yesd *Analysis not done. Login to comment 96 ABCC7 p.Leu997Phe ABCC7 p.Ile807Met DNA sequence identi®ed two CFTR mutations (I807M, L997F) in two subjects (14F and 15F respectively) and one 5T allele (12F). Login to comment 98 ABCC7 p.Gly551Asp ABCC7 p.Arg74Trp Three additional mutations in three female subjects were identi®ed by two other test methods: two mutations (DF508 and G551D) by the common mutation panel and one mutation (R74W) by CSGE. Login to comment 121 ABCC7 p.Arg117His ABCC7 p.Val201Met ABCC7 p.Trp1098Cys ABCC7 p.Pro750Leu ABCC7 p.Val520Ile ABCC7 p.Ile556Val ABCC7 p.Val456Ala ABCC7 p.Gln1352His ABCC7 p.Ile807Met Mutations and variants of unknown signi®cance detected in 16 patients with CAVD Detection method 31 common mutation panel and poly T analysis Sequence method and poly T analysis Mutations 5T 7 7 DF508 2 2 R117H 1 1 P750L ± 1 V201M ± 1 Q1352H ± 1 I556V ± 1 2752±26A®G ± 1 W1098C ± 1 I807M ± 1 V456A ± 1 V520I ± 1 Variants of unknown signi®cance 1717±4A®G ± 1 3601±3C®A ± 1 3499+25C®G ± 1 Total 10 22 the vas deferens is particularly susceptible to the decreased levels of CFTR protein product. Login to comment 124 ABCC7 p.Arg117His However, 5T in cis with certain mutations (i.e. R117H) may exert a more deleterious effect that contributes to disease phenotype. Login to comment 125 ABCC7 p.Arg117His For example, one patient in this series (DF508/R117H and one 5T allele) lost a brother to cystic ®brosis and reported that he has a personal history of a chronic cough, which could represent a mild CF phenotype. Login to comment 126 ABCC7 p.Trp1098Cys Another asymptomatic patient with CBAVD was found to be homozygous for the 5T allele in addition to carrying a W1098C mutation. Login to comment 143 ABCC7 p.Pro750Leu Results revealed that he carries the P750L mutation (not included in the common panel). Login to comment 144 ABCC7 p.Gly551Asp ABCC7 p.Arg74Trp ABCC7 p.Leu997Phe ABCC7 p.Ile807Met With this Table V. Description of female partners of CAVD patients and genetic results Subject no.a Ancestry Common mutation panel Sequence method CSGE method Interpretation Mutation panel/ CSGE/DNA sequence concordance 1F N.E. Cauc. Het. DF508 * * Mutation N/Ab 2F Asian Negative * Het. R74W Mutation No 3F Asian * Negative * No mutation detected Yes 4F Asian-Indian * Negative * No mutation detected Yes 5F Asian * Negative * No mutation detected Yes 6F N.E. Cauc./S.E.Cauc./ Ashkenazi Het. G551D * * Mutation N/Ab 7F Asian-Indian Negative Negative * No mutation detected Yes 8F Asian * Negative * No mutation detected Yes 9F Asian * Negative * No mutation detected Yes 10F S.E. Cauc./Ashkenazi * Negative * No mutation detected Yes 11F Hispanic * Negative * No mutation detected Yes 12F Asian * Negativec * No mutation detected Yes 13F Hispanic ² ² ² N/A N/A 14F S.E. Cauc./Asian * Het. L997F * Mutation Nod 15F Asian-Indian * Het. I807M * Mutation Nod 16F N.E. Cauc. Login to comment 164 ABCC7 p.Arg709* ABCC7 p.Val456Ala Mutation V456A (subject 7) has since been detected in three other symptomatic individuals, including: a Caucasian fetus with echogenic bowel, who has one other deleterious mutation, DF508; a Pakistani adult female with pulmonary symptoms and referred for CF testing who also harbors a DF508 mutation; and an Asian female infant with positive newborn screening and sweat tests, who has one other mutation, R709X. Login to comment 165 ABCC7 p.Val456Ala These clinical data from three compound heterozygotes provides compelling evidence that V456A is a genuine mutation. Login to comment 166 ABCC7 p.Ile807Met The second alteration involves I807M (subjects, 15 and 15F), detected in both our Asian-Indian patient and his consanguineous wife (they are ®rst cousins). Login to comment 168 ABCC7 p.Ile807Met The suspicion of I807M as a genuine mutation is also supported by the fact that the majority of amino acid-changing exonic alterations are deleterious and that most intronic sequence changes reported as deleterious are located within 10 base pairs of exons. Login to comment