title: A novel dominant mutation in SIX1, affecting a highly conserved residue, result in only auditory defects in humans.
abstract: Branchio-oto-renal (BOR) and Branchio-otic (BO) syndromes are dominant disorders characterized by variable hearing impairment (HI) and branchial defects. BOR includes additional kidney malformations. BO/BOR syndromes are genetically heterogeneous and caused by mutations in EYA1 and SIX1 genes. Mutation in SIX1 is responsible also for DFNA23, a locus for non-syndromic HI. Strikingly, the severity of the phenotype did not seem to correlate with the type of SIX1 mutation. Herein, we identified a novel mutation in SIX1 (p.E125K) in a Tunisian family with variable HI and preauricular pits. This mutation is located at the same position as the mutation identified in the Catwhesel (Cwe) mouse. No renal and branchial defects were observed in our family nor in Cwe/+ mice. A homology model revealed that the replacement of the Glutamate by a Lysine alters the electrostatic potential surface propriety which may affect the DNA-binding activity.
authors.affiliation: Equipe Procédés de Criblages Moléculaires et Cellulaires, Laboratoire de Microorganismes et de Biomolécules, Centre de Biotechnologie de Sfax, Université de Sfax, Tunisia.
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: Mosrati
authors.forename: Boutheina
authors.initials: B
authors.lastname: Hammami
authors.forename: Imen Ben
authors.initials: IB
authors.lastname: Rebeh
authors.forename: Leila
authors.initials: L
authors.lastname: Ayadi
authors.forename: Leila
authors.initials: L
authors.lastname: Dhouib
authors.forename: Khaireddine
authors.initials: K
authors.lastname: Ben Mahfoudh
authors.forename: Bochra
authors.initials: B
authors.lastname: Hakim
authors.forename: Ilhem
authors.initials: I
authors.lastname: Charfeddine
authors.forename: Jameleddine
authors.initials: J
authors.lastname: Mnif
authors.forename: Abdelmonem
authors.initials: A
authors.lastname: Ghorbel
authors.forename: Saber
authors.initials: S
authors.lastname: Masmoudi
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics; D017124:Conserved Sequence; D004423:Ear / Q000002:abnormalities*; D005260:Female; D034381:Hearing Loss / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D018398:Homeodomain Proteins; C099236:SIX1 protein, human