title: A clinical and molecular analysis of branchio-oculo-facial syndrome patients in Russia revealed new mutations in TFAP2A.
abstract: Branchio-oculo-facial syndrome (BOFS, OMIM# 113620) is a rare autosomal dominant disorder characterised by branchial cleft sinus defects, ocular anomalies and facial dysmorphisms, including lip or palate cleft or pseudocleft, and is associated with mutations in the TFAP2A gene. Here, we performed clinical analysis and mutation diagnostics in seven BOFS patients in Russia. The phenotypic presentation of BOFS observed in three patients showed high heterogeneity, including variation in its main clinical manifestations (linear loci of cervical cutaneous aplasia, ocular anomalies and orofacial cleft). In certain other cases, isolated ocular anomalies, or an orofacial cleft with accessory BOFS symptoms, were observed. In five BOFS patients, conductive hearing loss was diagnosed. Direct sequencing of the coding region of the TFAP2A gene revealed missense mutations in four BOFS patients. One patient was observed to have a previously described mutation (p.Arg251Gly), while three patients from two families were found to have novel mutations: p.Arg213Ser and p.Val210Asp. These novel mutations were not present in healthy members of the same family and therefore should be classified as de novo.
authors.affiliation: Scientific and Practical Centre of Medical Care for Children, Aviatorov Str., 38, Moscow, 119620, Russian Federation.
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Meshcheryakova
authors.forename: Rena A
authors.initials: RA
authors.lastname: Zinchenko
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Vasilyeva
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Marakhonov
authors.forename: Svetlana S
authors.initials: SS
authors.lastname: Zhylina
authors.forename: Nika V
authors.initials: NV
authors.lastname: Petrova
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Kozhanova
authors.forename: Maxim S
authors.initials: MS
authors.lastname: Belenikin
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Petrin
authors.forename: Gennady R
authors.initials: GR
authors.lastname: Mutovin
mesh_terms: D000293:Adolescent; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D012426:Russia; D050656:Transcription Factor AP-2; D055815:Young Adult
chemical_list: C493673:TFAP2A protein, human; D050656:Transcription Factor AP-2
keywords: Branchio-oculo-facial syndrome (BOFS); TFAP2A gene; cleft lip; cleft palate; mutation analysis