%0 Journal Article %J Am J Hum Genet %D 2013 %T Mutations in KCTD1 cause scalp-ear-nipple syndrome. %A Marneros, Alexander G %A Beck, Anita E %A Turner, Emily H %A McMillin, Margaret J %A Edwards, Matthew J %A Field, Michael %A de Macena Sobreira, Nara Lygia %A Perez, Ana Beatriz A %A Fortes, Jose A R %A Lampe, Anne K %A Giovannucci Uzielli, Maria Luisa %A Gordon, Christopher T %A Plessis, Ghislaine %A Le Merrer, Martine %A Amiel, Jeanne %A Reichenberger, Ernst %A Shively, Kathryn M %A Cerrato, Felecia %A Labow, Brian I %A Tabor, Holly K %A Smith, Joshua D %A Shendure, Jay %A Nickerson, Deborah A %A Bamshad, Michael J %K Abnormalities, Multiple %K Amino Acid Sequence %K Branchio-Oto-Renal Syndrome %K Co-Repressor Proteins %K Ear, External %K Ectodermal Dysplasia %K Exome %K Female %K Humans %K Hypospadias %K Male %K Molecular Sequence Data %K Muscle Hypotonia %K Mutation, Missense %K Nipples %K Pedigree %K Phenotype %K Protein Structure, Tertiary %K Repressor Proteins %K Scalp %K Sequence Homology, Amino Acid %X

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.

%B Am J Hum Genet %V 92 %P 621-6 %8 2013 Apr 04 %G eng %N 4 %1 https://www.ncbi.nlm.nih.gov/pubmed/23541344?dopt=Abstract %R 10.1016/j.ajhg.2013.03.002