Supplementary Information
Dupuis et al. Prevalence of Meconium ileus (MIP) marks the severity of mutations of the Cystic
Fibrosis Transmembrane Conductance Regulator (CFTR) gene
Content:
1. Supplementary Method
2. Supplementary Result: Table 1
3. Supplementary Result: Figure 1
Supplementary Method
The MI variable was validated across all participants from Toronto and the probability of meconium ileus
at birth according to the validated measure was modeled for participants with positive and negative MI
values in the database separately, controlling for age of diagnosis and the presence or absence of
siblings with CF.
Participants with a positive MI value in the database,
1. Among those with no CF siblings and an age of diagnosis greater than 3.5 months, the
probability of MI was taken from the model:
2. Those with at least one CF sibling and an age of diagnosis greater than 3.5 months were
excluded from analysis as we would expect that, under the circumstances, their age of diagnosis
should have been earlier
3. Where the age of diagnosis was less than 3.5 months, the probability of MI was taken to be 1.
Participants with a negative MI value in the database,
4. Among those with no CF siblings and an age of diagnosis less than 4 months, the probability of
MI was taken from:
5. Where age of diagnosis was greater than 4 months or the participant had at least one sibling
with CF, the probability of MI was taken to be 0.
Although the same equations were applied to all of the databases, data validation was only
performed for a subset of the Genome Canada database. It is possible that in the presence of
unusual combinations of variables, the error is not in the MI variable but rather, in recording family
history or age of diagnosis. For example, where the equation would increase the probability of MI in
a child with an early age of diagnosis and no family history based on information obtained in our
data validation phase, it is possible that in other databases, this same scenario would be indicative
of failure to report family history rather than unreported MI.
Supplementary Table 1
p. F508del / other
HGVS
Legacy name
c.1652G>A
c.1646G>A
c.532G>A
c.3752G>A
c.1645A>C or c.1647T>G
c.3731G>A
p.G551D
p.S549N
p.G178R
p.S1251N
p.S549R
p.G1244E
PIP
Canada
MIP
Canada
MIP
US
MIP
Germany
MIP
Italy
0.96 (54)
0.08 (53)
0.00 (3)
0.00 (4)
0.00 (1)
0.00 (2)
0.15 (979)
0.12 (39)
0.09 (22)
0.07 (14)
0.21 (14)
0.09 (84)
0.00 (1)
0.000 (3)
MIP scores (n=number of patients with the genotype) for all available class III CF-causing
variants are displayed including those with groups of CF patients <10 with the genotype.
Supplementary Figure 1
Correlation of MIP scores between the Canadian database and the US (n=20), German (n=7)
and North Italian database (n=10); n reflects the number of available CF-causing variants for
correlation analysis in each specific country group.