Is there a genetic predisposition to cystic fibrosis in individuals of Irish descent?

Genetic Predisposition for Cystic Fibrosis in Irish Descent Individuals

Yes, individuals of Irish descent have one of the highest genetic predispositions for cystic fibrosis worldwide, with a carrier frequency of approximately 1 in 25 and a disease incidence of 1 in 1461-2570. 1, 2

Epidemiology in Irish Populations

The genetic predisposition for cystic fibrosis (CF) in Irish populations is particularly notable:

• Historical data showed Ireland having the world's highest CF incidence at 1:1353 3
• More recent data from the National Newborn Screening program (2011-2017) revised this to 1:2570 2
• Carrier frequency in Irish populations is approximately 1:25 2
• This compares to European Caucasians generally having a carrier frequency of 1:29 4

Common CFTR Mutations in Irish Populations

The Irish population has a distinctive pattern of CFTR mutations:

• The ΔF508 (c.1521_1523delCTT) mutation is found in 72% of Irish CF chromosomes 1
• G551D (c.1652G>A) mutation occurs at 6.9% in Irish populations - the highest frequency reported worldwide 1
• R117H mutation occurs at 2% - also the highest reported frequency worldwide 1
• Recent newborn screening data found 55% of affected Irish newborns were homozygous for ΔF508 2
• 15% carried at least one copy of G551D mutation 2

Detection Rates and Testing

For individuals of Irish descent, genetic testing has important implications:

• Standard CF mutation panels can detect approximately 80-90% of mutations in European Caucasians 4
• Given the high prevalence of common mutations (ΔF508, G551D, R117H) in Irish populations, detection rates may be higher than in other European populations 1
• After a negative carrier test, the residual risk for European Caucasians is approximately 1 in 140 4

Clinical Implications

The high carrier rate in Irish populations has important clinical implications:

• 70% of affected Irish newborns are eligible for CFTR modulator treatment due to their specific mutation profile 2
• The high frequency of G551D mutation is particularly significant as it responds well to certain CFTR modulators
• Gender disparities have been noted in diagnosis, with longer delays in girls presenting with respiratory symptoms 3

Genetic Counseling Considerations

For individuals of Irish descent seeking genetic counseling:

• Carrier testing is particularly valuable given the high carrier rate
• Testing should include the common mutations found in Irish populations (ΔF508, G551D, R117H)
• Microsatellite haplotype analysis may be useful for genetic counseling in families with unidentified mutations 1
• Bayesian analysis should be used to calculate residual risk after negative testing, taking into account Irish ancestry 4

The high incidence of CF in Irish populations underscores the importance of considering genetic testing for individuals of Irish descent, particularly in preconception or prenatal settings, to identify carrier couples who may benefit from reproductive counseling.