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Genet Med. 2016 Apr;18(4):333-40. doi: 10.1038/gim.2015.79. Epub 2015 Jun 18.

Prevalence of meconium ileus marks the severity of mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene.

Author information

1
Clinical Research Services, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
2
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
3
Program in Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
4
Discipline of Paediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.
5
Department of Gastroenterology, Sydney Children's Hospital Randwick, New South Wales, Australia.
6
GeneYouIn Inc., Toronto, Ontario, Canada.
7
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
8
Department of Pediatrics, Justus-Liebig-University Giessen, Giessen, Germany.
9
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
10
Program in Genetics & Genome Biology, Research Institute, The Hospital for Sick Children and Division of Biostatistics.
11
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
12
Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.

Abstract

RATIONALE:

Meconium ileus (MI) is a perinatal complication in cystic fibrosis (CF), which is only minimally influenced by environmental factors. We derived and examined MI prevalence (MIP) scores to assess CFTR phenotype-phenotype correlation for severe mutations.

METHOD:

MIP scores were established using a Canadian CF population (n = 2,492) as estimates of the proportion of patients with MI among all patients carrying the same CFTR mutation, focusing on patients with p.F508del as the second allele. Comparisons were made to the registries from the US CF Foundation (n = 43,432), Italy (Veneto/Trentino/Alto Adige regions) (n = 1,788), and Germany (n = 3,596).

RESULTS:

The prevalence of MI varied among the different registries (13-21%). MI was predominantly prevalent in patients with pancreatic insufficiency carrying "severe" CFTR mutations. In this severe spectrum MIP scores further distinguished between mutation types, for example, G542X (0.31) with a high, F508del (0.22) with a moderate, and G551D (0.08) with a low MIP score. Higher MIP scores were associated with more severe clinical phenotypes, such as a lower forced expiratory volume in 1 second (P = 0.01) and body mass index z score (P = 0.04).

CONCLUSIONS:

MIP scores can be used to rank CFTR mutations according to their clinical severity and provide a means to expand delineation of CF phenotypes.Genet Med 18 4, 333-340.

PMID:
26087176
DOI:
10.1038/gim.2015.79
[Indexed for MEDLINE]

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