title: Homozygous CFTR mutation M348K in a boy with respiratory symptoms and failure to thrive. Disease-causing mutation or benign alteration?
abstract: We report on a 6-month-old premature boy from consanguineous parents. He presented with respiratory distress, necrotizing enterocolitis and hyperbilirubinemia shortly after birth. Persisting respiratory symptoms and failure to thrive prompted cystic fibrosis diagnostics, which showed the lack of wild-type signal for the mutation R347P suggesting a homozygous deletion or an alteration different from the known mutation at this position. Sequencing of this region revealed the homozygous substitution 1175 T > A (HGVS: c.1043 T > A) in exon 7 resulting in the homozygous amino acid change M348K. This mutation has never been reported in homozygosity before. Computational analysis tools classified M348K as 'presumably disease causing.' In our patient, sweat testing and electrophysiological assessment of CFTR function in native rectal epithelium demonstrated normal Cl(-) secretion.
  
  
  CONCLUSIONS
  We assume that the homozygous alteration M348K is a harmless variant rather than a CF-causing mutation.
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Kollegiengasse 10, 07743, Jena, Germany. julia.hentschel@mti.uni-jena.de
authors.forename: Julia
authors.initials: J
authors.lastname: Hentschel
authors.forename: Gabriele
authors.initials: G
authors.lastname: Riesener
authors.forename: Heike
authors.initials: H
authors.lastname: Nelle
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
authors.forename: Anja
authors.initials: A
authors.lastname: Schöner
authors.forename: Olaf
authors.initials: O
authors.lastname: Sommerburg
authors.forename: Eva
authors.initials: E
authors.lastname: Fritzsching
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
authors.forename: Ferdinand
authors.initials: F
authors.lastname: von Eggeling
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Mainz
mesh_terms: D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005183:Failure to Thrive / Q000209:etiology*; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D017354:Point Mutation; D012131:Respiratory Insufficiency / Q000209:etiology*
chemical_list: C505032:CFTR protein, human; D005819:Genetic Markers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator