ABCMdb

PMID: 16429424

Choi EH, Ehrmantraut M, Foster CB, Moss J, Chanock SJ
Association of common haplotypes of surfactant protein A1 and A2 (SFTPA1 and SFTPA2) genes with severity of lung disease in cystic fibrosis.
Pediatr Pulmonol. 2006 Mar;41(3):255-62., [PubMed]

Sentences

No. Mutations Sentence Comment

16 ABCC7 p.Ala455Glu So far, there has been no evidence to correlate common mutations in CFTR, particularly DF508, with pulmonary deterioration, the most common complication of CF.1,2 There are rare mutations, such as A455E, that appear to correlate with milder pulmonary disease.3 There is, however, a strong correlation between selective CFTR mutations and pancreatic disease.4,5 A wide variation in pulmonary disease within families harboring identical CFTR mutations has led many experts to postulate that environmental and secondary genetic factors, also known as modifying genes (CF modifiers), could be important.6,7 It was demonstrated in animal models that genetic modifiers can influence outcomes in CF: there was an observed difference in severity of both intestinal and lung disease between CF micewith different genetic backgrounds.8,9 A genetic linkage analysis suggested that a modifier gene for meconium ileus is located in the proximal region of mouse chromosome 7, which is syntenic with human chromosome 19q13.9,10 1 Section on Genomic Variation, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Login to comment 33 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg352Gln ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr Complementary mutations were identified in 51 CF subjects: R117H (4), R347H (1), R347P (1), G542X (7), G551D (4), 1717-1G-A (2), 2789 þ 5G > A(3), 3120 þ 1G > A (2), 3659delC (3), 3849 þ 10kbC>T (6), 394delTT (1), 621 þ 1G>T (4), 711 þ 1G > T (1), G85E (1), I507 (1), N1303K (2), R352Q (1), R553X (2), R560T (1), and W1282X (4). Login to comment 35 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gln493* Eleven subjects had rare mutations such as G551D/G551D, G551D/3659delC, G551D/I507, G551D/ Neg (2), E60X/Q493X, R1162X/G542X, W1282X/ W1282X (3), and 1717 À G > A/Neg. Login to comment 74 ABCC7 p.Ala455Glu None of the rare CFTR mutations previously associated with mild pulmonary disease, such as A455E, was included.3 There was no significant association between primary CFTR mutations and the following measured pulmonary parameters: FEV1, scores for ATS, AMA, dyspnea, physical grade, Shwachman-and Kulczycki, and PA colonization. Login to comment