Detection of an apparent homozygous 3120G>A cystic fibrosis mutation on a routine carrier screen.
A 28-year-old Caucasian female with no personal or family history of cystic fibrosis (CF) presented for preconception counseling and screening. Cystic fibrosis transmembrane conductance regulator (CFTR) mutation analysis using the Inno-LiPa CFTR assay revealed lack of hybridization for both the wild-type and mutant oligonucleotides for 3120+1G>A. This region was sequenced, and an apparent homozygous 3120G>A mutation was detected. Additional testing revealed an abnormal sweat chloride (77 mmol/L). Review of systems was essentially unremarkable with an absence of sinus symptoms, occasional nonproductive cough, and no features of malabsorption. Physical examination, chest X-ray, and pulmonary function tests were within normal limits. Only two other patients (siblings) with homozygous 3120G>A mutations have been reported (http://www.genet.sickkids.on.ca/cftr/). Both siblings had pancreatic insufficiency, mild pulmonary symptoms, and abnormal sweat chloride levels. Our findings suggest that a homozygous mutation of a G>A conversion at 3120 is associated with abnormal CFTR function and either a mild form of CF or no overt symptoms of disease, emphasizing the difficulties in assigning genotype/phenotype correlation.
Heaney
Denise LaMarche
DL
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 165 Ashley Ave., Suite 309, Charleston, SC 29425, USA. lamarche@musc.edu
Flume
Patrick
P
Hamilton
Lauren
L
Lyon
Elaine
E
Wolff
Daynna J
DJ
D000328:Adult; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype
D019005:Cystic Fibrosis Transmembrane Conductance Regulator