Non-classic cystic fibrosis associated with D1152H CFTR mutation.
BACKGROUND
Limited knowledge exists on phenotypes associated with the D1152H cystic fibrosis transmembrane conductance regulator (CFTR) mutation.


METHODS
Subjects with a D1152H allele in trans with another CFTR mutation were identified using the French Cystic Fibrosis Registry. Phenotypic characteristics were compared with those of pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) subjects in the Registry (CF cohort).


RESULTS
Forty-two subjects with D1152H alleles were identified. Features leading to diagnosis included chronic sinopulmonary disease (n = 25), congenital absence of the vas deferens (n = 11), systematic neonatal screening (n = 4), and genetic counseling (n = 2). Median age at diagnosis was 33 [interquartile range (IQR, 24-41)] years in D1152H subjects. Median sweat chloride concentrations were 43.5 (39-63) mmol/l in D1152H subjects and were markedly lower than in PI and PS CF subjects (p < 0.05). Bronchiectasis was present in 67% of D1152H subjects, but Pseudomonas aeruginosa colonization and pancreatic insufficiency were present in <30% of subjects. Estimated rates of decline in forced expiratory volume in 1 s (FEV(1)) were lower in D1152H subjects vs PI CF subjects (p < 0.05). None of the D1152H subjects identified since 1999 had died or required lung transplantation.


CONCLUSIONS
When present in trans with a CF-causing mutation, D1152H causes significant pulmonary disease, but all subjects had prolonged survival.
Burgel
P-R
PR
Hôpital Cochin, APHP, Université Paris Descartes, Paris, France. pierre-regis.burgel@cch.aphp.fr
Fajac
I
I
Hubert
D
D
Grenet
D
D
Stremler
N
N
Roussey
M
M
Siret
D
D
Languepin
J
J
Mely
L
L
Fanton
A
A
Labbé
A
A
Domblides
P
P
Vic
P
P
Dagorne
M
M
Reynaud-Gaubert
M
M
Counil
F
F
Varaigne
F
F
Bienvenu
T
T
Bellis
G
G
Dusser
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002712:Chlorides / Q000032:analysis; D015331:Cohort Studies; D032921:Consensus; D003550:Cystic Fibrosis / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009297:Nasal Mucosa / Q000503:physiopathology; D013542:Sweat / Q000737:chemistry; D055815:Young Adult
D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator