A lot of new parents want to understand exactly what the future holds for their CFer. Although a lot of info has been gathered regarding genotype and phenotype the data has only served to generate some "rules of thumb".
1989+1G>A is an mRNA splicing type gene. These are typically classified as Class I type mutations. Class I mutations lead to defects in the synthesis of stable CFTR mRNA transcripts resulting in absence of the CFTR protein. About half of all mutations in CFTR (encompassing premature termination, exon skipping, aberrant mRNA splicing, and frameshifts) are thought to fall into this class and result in complete loss of CFTR protein/function.
The other gene also plays a part. In short, a Class I-II/I-II combination is typically associated with a poor clinical outcome (i.e. lower PFT, PI, and a lower probability of survival). Where as someone with a I-II/III, I-II/IV or I-II/V is typically associated with less severe symptoms and in general a more favorable clinical outcome.
<div class="FTQUOTE"><begin quote>Genotype-phenotype correlation for pulmonary function in cystic fibrosis.de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E.
Department of Pneumology, Hospital general Vall d'Hebron, Barcelona, Spain. jgracia@separ.es
BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.</end quote></div>
Of course, we have plenty of people on the forum here that have the same genotypes but completely different clinical outcomes. Environment, compliance, quality of care, and luck all contribute to clinical outcome. So, as I stated, the above are simply rules of thumb.
