Genetic and developmental lung disease Flashcards
Name 2 Respiratory conditions caused by the alteration of a single gene
- Cystic Fibrosis (CF) - >1500 mutations identified in CFTR gene
- Alpha 1 anti trypsin deficiency (A1AT) - aka a1-proteinase inhibitor (PI) deficiency. SERPINA1 gene.
antitrypsin). Mutation SNP G-342A in >90% of cases
In other diseases facts, such as geographical distribution or familial clusters, indicate a genetic background. This is the case in asthma, sarcoidosis, pulmonary fibrosis and primary pulmonary hypertension
Which gene locus is implicated in susceptibility to Chronic Beryllium Disease (CBD)?
HLA-DPB1 gene.
Glutamine at position 69 in the HLA-DPB1 gene does not cause illness; but when in contact with beryllium
dust, carriers of Glu69+ HLA-DPB1 are at increased risk of developing chronic beryllium disease (CBD).
Up to 97% of CBD patients are Glu69+ HLA-DPB1 positive.
What is the most common genetic defect in patients with Cystic Fibrosis?
The most common defect is the deletion of a phenylalanine at position 508 (DF508), which is responsible for up to 70% of all CF cases. There are >150 mutations, some with milder phenotypes. There is marked variation in frequency of different mutations in different populations.
DF508 - 1:2000 in Caucasians esp Scotland, and the Faroe Islands (1:500). Lower in descendants from Africa (1:15 000); and lowest in Asians (1:30 000).
What is the Z allele in alpha 1 anti trypsin deficiency?
The Z allele is a common mutation in the alpha-1 proteinase (antitrypsin) gene, in 90% of cases of the disease this is the single mutation. The mutation is a glycine to leucine substitution at position 342. This leads to a structural change which affects post-translation modifications and secretion of the protein. The Z allele leads to a reduction in alpha1 levels to <15% in serum.
Up to 4% of European populations are heterozygous for the Z allele, whereas it is much rarer eg in African Americans 0.4%
