title: A new hereditary congenital facial palsy case supports arg5 in HOX-DNA binding domain as possible hot spot for mutations.
abstract: Moebius syndrome (MBS) is a rare congenital disorder characterized by rhombencephalic mal development, mainly presenting with facial palsy with limited gaze abduction. Most cases are sporadic, possibly caused by a combination of environmental and genetic factors; however, no proven specific associations have been yet established. Hereditary congenital facial palsy (HCFP) is an autosomal dominant congenital dysinnervation syndrome, recognizable by the isolated dysfunction of the seventh cranial nerve. Mutant mice for Hoxb1 were reported to present with facial weakness, resembling MBS. Recently a homozygous mutation altering arg5 residue of HOXB1 homeodomain into cys5 was identified in two families with HCFP. We screened 95 sporadic patients diagnosed as MBS or HCFP for mutations in HOXB1. A novel homozygous alteration was identified in one HCFP case, affecting the same residue, resulting to his5. In silico protein analysis predicted stronger HOXB1-DNA binding properties for his5 than cys5 that resulted to milder phenotype. It should be noted that, inclusive of the previous report, only two mutations revealed in HOXB1 associated with HCFP involved the same amino acid arg5 in HOXB1 residing in HOXB1-DNA-PBX1 ternary complex.
authors.affiliation: Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, 34093 Turkey. Electronic address: o.uyguner@istanbul.edu.tr.
authors.forename: Zehra Oya
authors.initials: ZO
authors.lastname: Uyguner
authors.affiliation: Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, 34093 Turkey.
authors.forename: Güven
authors.initials: G
authors.lastname: Toksoy
authors.affiliation: Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, 34093 Turkey.
authors.forename: Umut
authors.initials: U
authors.lastname: Altunoglu
authors.affiliation: Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, 34093 Turkey.
authors.forename: Hilal
authors.initials: H
authors.lastname: Ozgur
authors.affiliation: Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, 34093 Turkey.
authors.forename: Seher
authors.initials: S
authors.lastname: Basaran
authors.affiliation: Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, 34093 Turkey.
authors.forename: Hülya
authors.initials: H
authors.lastname: Kayserili
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics; D001665:Binding Sites; D003545:Cysteine / Q000235:genetics; D005158:Facial Paralysis / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006639:Histidine / Q000235:genetics; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007223:Infant; D020331:Mobius Syndrome / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: C101121:HOXB1 homeodomain protein; D018398:Homeodomain Proteins; D006639:Histidine; D001120:Arginine; D003545:Cysteine
keywords: HOXB1; Hereditary congenital facial palsy; Moebius syndrome