ABCMdb

PMID: 20494257

Dungan JS
Carrier screening for cystic fibrosis.
Obstet Gynecol Clin North Am. 2010 Mar;37(1):47-59, Table of Contents., [PubMed]

Sentences

No. Mutations Sentence Comment

58 ABCC7 p.Arg117His When found in cis to the R117H mutation, (ie, is on the same chromosome), the effect can be identical to a ''severe`` mutation, and thus if this combination exists in conjunction with a classic CFTR mutation, one would predict full manifestations of classic CF. Login to comment 59 ABCC7 p.Arg117His If the R117H mutation exists with the normal 7T (or 9T) allele, the effect is dampened. Login to comment 63 ABCC7 p.Arg117His However, it is important to perform poly-T analysis if the R117H mutation is identified, as this combination (in cis) is considered a ''severe`` CF mutation. Login to comment 102 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr However, in instances of a positive family history of affected individuals, but with no known mutation, further Table 2 Mutation panel recommended by ACOG and ACMG (listed in order of decreasing frequency in non-Hispanic Caucasian population) F508 del delI507 R347P R1162X G542X R553X 71111G>T 2184delA G551D R117H R560T 189811G>A 62111G>T 3849110kbC>T 3569delC R334W W1282X 1717À1G>T A455E 312011G>T N1303K 278915G>A G85E Data from Watson MS, Cutting GR, Desnick RJ, et al. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Login to comment 111 ABCC7 p.Arg117His The ACMG guidelines on CF carrier testing state that intron 8 poly-T analysis should be reported only as a reflex if the R117H allele is found (see section on ''severe`` versus ''mild`` alleles). Login to comment 112 ABCC7 p.Arg117His Despite the lack of predictable or consistent phenotype associated with the 5T intron 8 allele in conjunction with any mutation other than R117H, a considerable number of laboratories performing carrier testing for CF in the United States still report the 5T allele on all specimens.16 This activity has led to unnecessary invasive prenatal testing whereby parents are not at risk of having a child with CF, and misunderstand the significance (or lack thereof) of the 5T allele.17,18 While such situations are generally rare, these events reflect the complexity of carrier testing strategies for this particular disorder, and the continued need for provider education. Login to comment 150 ABCC7 p.Ile148Thr The Society of Obstetricians and Gynaecologists of Canada has stated routine CF carrier screening ''cannot be recommended at this time.``22 Two mutations were subsequently deleted from the original 2001 recommendation as a result of further epidemiologic data.13 The I148T mutation was subsequently found not to be disease causing (it was originally considered so because of the erroneous perception of its frequent appearance with 3199del6, a rare, but confirmed CF mutation). Login to comment