A.2. A.2.1. CF is usually clinically diagnosed with supporting evidence of a CFTR abnormality, either by sweat chloride measurement or identification of mutations in the CFTR gene known to cause CF. An elevated immunoreactive trypsinogen (IRT) level during screening can replace clinical features as a diagnostic criterion in newborns (see page 38). Diagnosis is usually simple following NBS or clinical presentation with an elevated sweat chloride level, but in some situations the combined information makes the diagnosis difficult, for example mild symptoms, a (borderline) positive sweat test, or a new CFTR sequence variation of unknown significance (). As stated previously, diagnostic testing for hereditary mutations in the CFTR gene occurs in three distinct groups/indications: in people with a high clinical suspicion of CF for prenatal CF diagnosis in partners of people with known CFTR mutations for the purpose of reproductive planning. The first group includes individuals presenting with classic or non-classic CF symptoms (including men with CBAVD). Prenatal diagnosis would be indicated for couples who have had a previous child with CF or a CFTR-related disorder, or who have been identified by other means to both be carriers of a CFTR mutation. It could also be used in cases where the fetus is found to have an ‘echogenic gut’. In this scenario the fetus’s parents would undergo CFTR mutation testing to determine if they are carriers, prior to the fetus being tested (if both parents are found to be carriers). The third group includes the testing of a partner of someone with at least one known CFTR mutation, which would influence their reproductive planning to allow an additional option of pre-implantation genetic diagnosis (PGD) if both partners have at least one CFTR mutation. Each person or fetus being tested for hereditary mutations in the CFTR gene would only need to be tested once in their lifetime. Most CF patients would be diagnosed through NBS (see page 38), and the ultrasound examination showing ‘echogenic gut’ leads to approximately 11% of CF diagnoses (). A small percentage of patients are diagnosed when older, as they often have a milder form of the disease (such as men with CBAVD). Different gene tests The common CFTR tests are: F508del mutation single mutation common mutation poly-T (for mild disease and infertility)
A.2. A.2.1. CF is usually clinically diagnosed with supporting evidence of a CFTR abnormality, either by sweat chloride measurement or identification of mutations in the CFTR gene known to cause CF. An elevated immunoreactive trypsinogen (IRT) level during screening can replace clinical features as a diagnostic criterion in newborns (see page 38). Diagnosis is usually simple following NBS or clinical presentation with an elevated sweat chloride level, but in some situations the combined information makes the diagnosis difficult, for example mild symptoms, a (borderline) positive sweat test, or a new CFTR sequence variation of unknown significance (). As stated previously, diagnostic testing for hereditary mutations in the CFTR gene occurs in three distinct groups/indications: in people with a high clinical suspicion of CF for prenatal CF diagnosis in partners of people with known CFTR mutations for the purpose of reproductive planning. The first group includes individuals presenting with classic or non-classic CF symptoms (including men with CBAVD). Prenatal diagnosis would be indicated for couples who have had a previous child with CF or a CFTR-related disorder, or who have been identified by other means to both be carriers of a CFTR mutation. It could also be used in cases where the fetus is found to have an ‘echogenic gut’. In this scenario the fetus’s parents would undergo CFTR mutation testing to determine if they are carriers, prior to the fetus being tested (if both parents are found to be carriers). The third group includes the testing of a partner of someone with at least one known CFTR mutation, which would influence their reproductive planning to allow an additional option of pre-implantation genetic diagnosis (PGD) if both partners have at least one CFTR mutation. Each person or fetus being tested for hereditary mutations in the CFTR gene would only need to be tested once in their lifetime. Most CF patients would be diagnosed through NBS (see page 38), and the ultrasound examination showing ‘echogenic gut’ leads to approximately 11% of CF diagnoses (). A small percentage of patients are diagnosed when older, as they often have a milder form of the disease (such as men with CBAVD). Different gene tests The common CFTR tests are: F508del mutation single mutation common mutation poly-T (for mild disease and infertility)
1216-MSAC-CA-CFTR.docx