Mutations in KCTD1 cause scalp-ear-nipple syndrome.

TitleMutations in KCTD1 cause scalp-ear-nipple syndrome.
Publication TypeJournal Article
Year of Publication2013
AuthorsMarneros, AG, Beck, AE, Turner, EH, McMillin, MJ, Edwards, MJ, Field, M, Sobreira, NLygia de M, Perez, ABeatriz A, Fortes, JAR, Lampe, AK, Uzielli, MLuisa Giov, Gordon, CT, Plessis, G, Le Merrer, M, Amiel, J, Reichenberger, E, Shively, KM, Cerrato, F, Labow, BI, Tabor, HK, Smith, JD, Shendure, J, Nickerson, DA, Bamshad, MJ
Corporate AuthorsUniversity of Washington Center for Mendelian Genomics
JournalAm J Hum Genet
Date Published2013 Apr 4
KeywordsAbnormalities, Multiple, Amino Acid Sequence, Branchio-Oto-Renal Syndrome, Ear, External, Ectodermal Dysplasia, Exome, Female, Humans, Hypospadias, Male, Molecular Sequence Data, Muscle Hypotonia, Mutation, Missense, Nipples, Pedigree, Phenotype, Protein Structure, Tertiary, Repressor Proteins, Scalp, Sequence Homology, Amino Acid

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.

Alternate JournalAm. J. Hum. Genet.
PubMed ID23541344
PubMed Central IDPMC3617379
Grant List1RC2HG005608 / HG / NHGRI NIH HHS / United States
1U54HG006493 / HG / NHGRI NIH HHS / United States
5R01HG004316 / HG / NHGRI NIH HHS / United States
K23 HD057331 / HD / NICHD NIH HHS / United States
R01 HD048895 / HD / NICHD NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States