title: Mutations in KCTD1 cause scalp-ear-nipple syndrome.
abstract: Scalp-ear-nipple (SEN) syndrome is a rare, autosomal-dominant disorder characterized by cutis aplasia of the scalp; minor anomalies of the external ears, digits, and nails; and malformations of the breast. We used linkage analysis and exome sequencing of a multiplex family affected by SEN syndrome to identify potassium-channel tetramerization-domain-containing 1 (KCTD1) mutations that cause SEN syndrome. Evaluation of a total of ten families affected by SEN syndrome revealed KCTD1 missense mutations in each family tested. All of the mutations occurred in a KCTD1 region encoding a highly conserved bric-a-brac, tram track, and broad complex (BTB) domain that is required for transcriptional repressor activity. KCTD1 inhibits the transactivation of the transcription factor AP-2α (TFAP2A) via its BTB domain, and mutations in TFAP2A cause cutis aplasia in individuals with branchiooculofacial syndrome (BOFS), suggesting a potential overlap in the pathogenesis of SEN syndrome and BOFS. The identification of KCTD1 mutations in SEN syndrome reveals a role for this BTB-domain-containing transcriptional repressor during ectodermal development.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Marneros
authors.forename: Anita E
authors.initials: AE
authors.lastname: Beck
authors.forename: Emily H
authors.initials: EH
authors.lastname: Turner
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: McMillin
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: Michael
authors.initials: M
authors.lastname: Field
authors.forename: Nara Lygia
authors.initials: NL
authors.lastname: de Macena Sobreira
authors.forename: Ana Beatriz A
authors.initials: AB
authors.lastname: Perez
authors.forename: Jose A R
authors.initials: JA
authors.lastname: Fortes
authors.forename: Anne K
authors.initials: AK
authors.lastname: Lampe
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Giovannucci Uzielli
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Gordon
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Plessis
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.forename: Ernst
authors.initials: E
authors.lastname: Reichenberger
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Shively
authors.forename: Felecia
authors.initials: F
authors.lastname: Cerrato
authors.forename: Brian I
authors.initials: BI
authors.lastname: Labow
authors.forename: Holly K
authors.initials: HK
authors.lastname: Tabor
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Smith
authors.forename: Jay
authors.initials: J
authors.lastname: Shendure
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bamshad
mesh_terms: D000015:Abnormalities, Multiple / Q000209:etiology* / Q000473:pathology; D000595:Amino Acid Sequence; D019280:Branchio-Oto-Renal Syndrome / Q000209:etiology* / Q000473:pathology; D056970:Co-Repressor Proteins; D004431:Ear, External / Q000002:abnormalities / Q000473:pathology; D004476:Ectodermal Dysplasia / Q000209:etiology* / Q000473:pathology; D059472:Exome / Q000235:genetics*; D005260:Female; D006801:Humans; D007021:Hypospadias / Q000209:etiology* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009123:Muscle Hypotonia / Q000209:etiology* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D009558:Nipples / Q000002:abnormalities / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics*; D012535:Scalp / Q000002:abnormalities / Q000473:pathology; D017386:Sequence Homology, Amino Acid
chemical_list: D056970:Co-Repressor Proteins; C529677:KCTD1 protein, human; D012097:Repressor Proteins
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