PMID- 32483343
OWN - NLM
STAT- MEDLINE
DCOM- 20210602
LR  - 20211203
IS  - 1476-5438 (Electronic)
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 28
IP  - 12
DP  - 2020 Dec
TI  - National Newborn Screening for cystic fibrosis in the Republic of Ireland: 
      genetic data from the first 6.5 years.
PG  - 1669-1674
LID - 10.1038/s41431-020-0661-5 [doi]
AB  - Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disease 
      in the Republic of Ireland (ROI), with a previously quoted incidence of 1 in 1353 
      and carrier rate of 1 in 19. The National Newborn Screening (NBS) for CF was 
      incorporated in July 2011 in the ROI. A cut-off point of the top 1% 
      Immunoreactive Trypsinogen (IRT) was taken as an indication for 38 CFTR variant 
      panel to maximise identification of affected CF cases and to minimise detection 
      of carriers. All neonates from July 2011 to Dec 2017 with an elevated IRT on NBS 
      were tested with 38 CFTR mutation panel and included. Clinical and laboratory 
      database were analysed. In the first 6.5 years a total of 5,053 newborns (1.16% 
      of total births) were screened with 38 CFTR panel. 170 CF affected cases, 320 
      unaffected carriers, 32 CF Screening Positive Inconclusive Diagnosis (CFSPID) 
      were identified. There was one missed diagnosis. The most common disease-causing 
      variant was c.1521_1523delCTT (p.(Phe508del)) followed by c.1652G>A 
      (p.(Gly551Asp)). 95 out of 170 (55%) affected newborns were homozygous for 
      c.1521_1523delCTT (p.(Phe08del)) and 25 (15%) carried at least one copy of 
      c.1652G>A (p.(Gly551Asp)). Hence, 70% of affected newborns were eligible for CFTR 
      modulator treatment. The NBS programme has identified almost triple the number of 
      affected newborn with c.1652G>A (p.(Gly551Asp)) than previously quoted figures 
      and identified less than 50% of carriers than predicted. The revised incidence 
      and carrier frequency of CF in the ROI is 1 in 2570 and 1 in 25, respectively.
FAU - Sasaki, Erina
AU  - Sasaki E
AUID- ORCID: 0000-0003-1448-1151
AD  - Department of Clinical Genetics, Children's Health Ireland (CHI) at Crumlin, 
      Dublin, Ireland. sasakierina06@gmail.com.
FAU - Kostocenko, Marija
AU  - Kostocenko M
AD  - Department of Clinical Genetics, Children's Health Ireland (CHI) at Crumlin, 
      Dublin, Ireland.
AD  - Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland.
FAU - Lang, Niamh
AU  - Lang N
AD  - Department of Clinical Genetics, Children's Health Ireland (CHI) at Crumlin, 
      Dublin, Ireland.
FAU - Clark, Tara
AU  - Clark T
AD  - Department of Clinical Genetics, Children's Health Ireland (CHI) at Crumlin, 
      Dublin, Ireland.
FAU - Rogers, Melissa
AU  - Rogers M
AD  - Department of Clinical Genetics, Children's Health Ireland (CHI) at Crumlin, 
      Dublin, Ireland.
FAU - Muldowney, Rebecca
AU  - Muldowney R
AD  - Department of Clinical Genetics, Children's Health Ireland (CHI) at Crumlin, 
      Dublin, Ireland.
FAU - Walsh, Olivia
AU  - Walsh O
AD  - Newborn Bloodspot Screening Laboratory, Department of Paediatric Laboratory 
      Medicine, Children's Health Ireland (CHI) at Temple Street, Dublin, Ireland.
FAU - O'Grady, Loretta
AU  - O'Grady L
AD  - Newborn Bloodspot Screening Laboratory, Department of Paediatric Laboratory 
      Medicine, Children's Health Ireland (CHI) at Temple Street, Dublin, Ireland.
FAU - Edge, Gillian
AU  - Edge G
AD  - Newborn Bloodspot Screening Laboratory, Department of Paediatric Laboratory 
      Medicine, Children's Health Ireland (CHI) at Temple Street, Dublin, Ireland.
FAU - Ward, Alana
AU  - Ward A
AD  - Department of Clinical Genetics, Children's Health Ireland (CHI) at Crumlin, 
      Dublin, Ireland.
FAU - Linnane, Barry
AU  - Linnane B
AD  - Graduate Entry Medical School and Centre for Interventions in Infection, 
      Inflammation and Immunity [4i], University of Limerick, Limerick, Ireland.
AD  - National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, 
      Dublin, Ireland.
FAU - Borovickova, Ingrid
AU  - Borovickova I
AD  - Newborn Bloodspot Screening Laboratory, Department of Paediatric Laboratory 
      Medicine, Children's Health Ireland (CHI) at Temple Street, Dublin, Ireland.
FAU - Barton, David E
AU  - Barton DE
AUID- ORCID: 0000-0002-2031-9719
AD  - Department of Clinical Genetics, Children's Health Ireland (CHI) at Crumlin, 
      Dublin, Ireland.
FAU - Lynch, Sally Ann
AU  - Lynch SA
AD  - Department of Clinical Genetics, Children's Health Ireland (CHI) at Crumlin, 
      Dublin, Ireland.
LA  - eng
PT  - Journal Article
DEP - 20200601
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (CFTR protein, human)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
SB  - IM
CIN - Eur J Hum Genet. 2020 Oct;28(10):1305-1306. PMID: 32661329
MH  - Cystic Fibrosis/diagnosis/*genetics
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/*genetics
MH  - Female
MH  - Gene Frequency
MH  - Genetic Testing/standards/*statistics & numerical data
MH  - Heterozygote
MH  - Humans
MH  - Infant, Newborn
MH  - Ireland
MH  - Male
MH  - Mutation
MH  - Neonatal Screening/*standards
MH  - Sensitivity and Specificity
PMC - PMC7784902
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/06/03 06:00
MHDA- 2021/06/03 06:00
PMCR- 2021/12/01
CRDT- 2020/06/03 06:00
PHST- 2019/11/28 00:00 [received]
PHST- 2020/05/19 00:00 [accepted]
PHST- 2020/05/05 00:00 [revised]
PHST- 2020/06/03 06:00 [pubmed]
PHST- 2021/06/03 06:00 [medline]
PHST- 2020/06/03 06:00 [entrez]
PHST- 2021/12/01 00:00 [pmc-release]
AID - 10.1038/s41431-020-0661-5 [pii]
AID - 661 [pii]
AID - 10.1038/s41431-020-0661-5 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 2020 Dec;28(12):1669-1674. doi: 10.1038/s41431-020-0661-5. Epub 
      2020 Jun 1.