ABCMdb

PMID: 15952991

Highsmith WE Jr, Friedman KJ, Burch LH, Spock A, Silverman LM, Boucher RC, Knowles MR
A CFTR mutation (D1152H) in a family with mild lung disease and normal sweat chlorides.
Clin Genet. 2005 Jul;68(1):88-90., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Asp1152His Letter to the Editor A CFTR mutation (D1152H) in a family with mild lung disease and normal sweat chlorides To the Editor: Over 1000 mutations in the cystic fibrosis transmembrane regulator (CFTR) gene have been reported to cause cystic fibrosis (CF); however, only a few are associated with mild disease (1, 2). Login to comment 1 ABCC7 p.Asp1152His We report a novel mutation (D1152H) in three siblings with unusually mild CF, surviving past age 64 with pancreatic exocrine sufficiency, normal sweat chloride (Cl- ) concentrations, and reduced CFTR-mediated Cl-conductance across the nasal epithelium. Login to comment 3 ABCC7 p.Asp1152His This nucleotide change results in an aspartic acid to histidine substitution at position 1152 of the mature protein (D1152H). Login to comment 15 ABCC7 p.Gly542* ABCC7 p.Asp1152His The three siblings with the clinical syndrome of CF were compound heterozygotes, D1152H/G542X. Login to comment 22 ABCC7 p.Asp1152His ABCC7 p.Asp1152His Recent work by Vankeerberghen et al. has demonstrated reduced whole cell Cl- currents when a D1152H-bearing CFTR cDNA is expressed in Xenopus oocytes, confirming that D1152H is a type IV mutation (9). Login to comment 23 ABCC7 p.Asp1152His Since our initial report to the Cystic Fibrosis Gene Analysis Consortium (10, 11), D1152H has been detected frequently in men with congenital bilateral absence of vas deferens (CBAVD) from three continents (12-16). Login to comment 24 ABCC7 p.Asp1152His One large study found D1152H to be the fourth most common CFTR mutation in men with CBAVD (17). Login to comment 29 ABCC7 p.Gly542* ABCC7 p.Asp1152His The lung disease attributable to the D1152H/G542X genotype in this family, even with the additional insult of prolonged smoking, is associated with survival into the seventh and eighth decade of life. Login to comment 34 ABCC7 p.Asp1152His The frequent appearance of this mutation among CBAVD men, and now in very mild CF, highlights the prevalence of D1152H and suggests it is sufficiently common to warrant further research and potentially a higher clinical profile. Login to comment 36 ABCC7 p.Asp1152His Sweat gland and nasal epithelial physiologic properties in two siblings with cystic fibrosis and the D1152H mutation Sweat glanda Nasal bioelectric propertiesb Patients Sweat duct PDc (mV) Secretion after isoproterenold (nl/min/gland) Mean PD (mV) Maximal PD (mV) Amiloride inhibition (%) Cl- diffusion PD (mV) Isoproterenol augmentation (mV) 1 À41 0 À41 À46 75 þ2 Not done 2 Not done 0 À21 À24 57 þ1 À5 Normal subjects À10 to À45 0.2-3.0 À21.7 Æ 6.1 À32.5 Æ 6.1 56.6 Æ 15.5 À16.7 Æ 6.6 À16.0 Æ 6.1 Cystic fibrosis À45 to À80 0 À47.7 Æ 6.5 À67.5 Æ 9.8 74.8 Æ 8.0 þ5.3 Æ 1.6 À0.1 Æ 1.1 Cl- , chloride; PD, potential difference. Login to comment 86 ABCC7 p.Asp1152His Friedman KJ, Highsmith WE Jr, Zhou Z et al. D1152H: a common CFTR mutation associated with highly variable disease expression. Login to comment