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Novel cystic fibrosis mutation L1093P: Functional analysis and possible Native American origin
Author(s) -
Yee Kevin,
Robinson Clare,
Hurlock Gregory,
Moss Richard B.,
Wine Jeffrey J.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(200002)15:2<208::aid-humu17>3.0.co;2-6
Subject(s) - biology , missense mutation , cystic fibrosis , genetics , mutation , heteroduplex , microbiology and biotechnology , exon , mutation testing , gene
A novel mutation was detected using single‐strand conformation polymorphism and heteroduplex analysis in a cystic fibrosis subject of mixed ancestry. Mutation 3410T→C in exon 17b caused the novel missense mutation L1093P; the other chromosome has mutation N1303K. The 31‐year‐old subject is pancreatic insufficient, had an FEV 1 score that was 33% of normal prior to a heart/lung transplant, and sweat chloride values of 116 and 95 mM when tested at ages 1 and 11. Functional analysis using forskolin‐stimulated efflux of 125 I in HEK cells transfected with an ABCC7 construct harboring the L1093P mutation confirmed that cAMP‐mediated anion efflux was abnormal, but some function was preserved. Analysis of parental DNA established that N1303K was of English origin, while L1093P was of Greek, Irish or Native American (Cherokee) origin. Given the intensive screening for CF mutations in European populations, we hypothesize that L1093P is of Native American origin. Hum Mutat 15:208, 2000. © 2000 Wiley‐Liss, Inc.