ABCMdb

PMID: 22256939

Massie RJ, Curnow L, Glazner J, Armstrong DS, Francis I
Lessons learned from 20 years of newborn screening for cystic fibrosis.
Med J Aust. 2012 Jan 16;196(1):67-70., [PubMed]

Sentences

No. Mutations Sentence Comment

14 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Val520Phe ABCC7 p.Val520Phe ABCC7 p.Arg560Thr ABCC7 p.Arg560Thr From 1991 to 2006, babies with an IRT level > 99th percentile had CFTR gene mutation analysis for p.F508del and, from 2007, for 12 CFTR mutations (p.F508del, p.G551D, p.G542X, p.N1303K, c.1585- 1G>A, p.I507del, p.R560T, p.W1282X, p.V520F, c.489+1G>T, p.R553X, c.3718-2477C>T). Login to comment 30 ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Arg1162* ABCC7 p.Ser549Asn Where possible, all patients with a diagnosis of CF had further CFTR mutation analysis performed in an attempt to clarify the genotype (p.A455E, p.S549N, p.R347H, p.R1162X, p.R347P, p.R334W, p.R117H). Login to comment 59 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ◆ 69MJA 196 (1) · 16 January 2012 Changing the CFTR mutation panel from p.F508del alone to 12 mutations resulted in the detection of one child (mutation p.G551D/unknown) who would have been missed by the previous screening protocol. Login to comment 94 ABCC7 p.Arg117His The term CFTR-related metabolic syndrome has been developed in the US to allow a systematic approach to follow-up of these infants.15 Many years of clinical follow-up with repeat sweat tests and more extensive CFTR genotype analyses will be required to establish how many of these infants have CF.10,16 Other lessons learned from our screening program include the lack of value in testing infants with a markedly elevated initial IRT level in the absence of a CFTR mutation - a practice advocated by some centres.17 We have previously demonstrated the difficulty of including the R117H mutation in the screening panel, and deliberately avoided it in our newborn screening and carrier screening programs.18-20 This decision has been supported by French data highlighting the low penetrance of this mutation.21 In addition, we have shown a modest reduction in the live-birth prevalence of CF since the introduction of screening, because families use prenatal testing for subsequent pregnancies.22,23 Emerging issues in newborn screening have been well described in a recent review.24 Of key importance to Australia is whether newborn screening strategies should switch to IRT/pancreatitis-associated peptide to avoid detection of carriers altogether.25 There are a number of trials of this in progress around the world, including in South Australia. Login to comment 137 ABCC7 p.Arg117His Genetic counselling after carrier detection by newborn screening when one parent carries DeltaF508 and the other R117H. Login to comment 139 ABCC7 p.Arg117His ABCC7 p.Arg117Cys 19 Massie RJ, Poplawski N, Wilcken B, et al. Intron-8 polythymidine sequence in Australasian individuals with CF mutations R117H and R117C. Login to comment 140 ABCC7 p.Arg117His Genetic counselling after carrier detection by newborn screening when one parent carries DeltaF508 and the other R117H. Login to comment 142 ABCC7 p.Arg117His ABCC7 p.Arg117Cys 19 Massie RJ, Poplawski N, Wilcken B, et al. Intron-8 polythymidine sequence in Australasian individuals with CF mutations R117H and R117C. Login to comment 144 ABCC7 p.Arg117His 21 Thauvin-Robinet C, Munck A, Huet F, et al. The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening. Login to comment 147 ABCC7 p.Arg117His 21 Thauvin-Robinet C, Munck A, Huet F, et al. The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening. Login to comment