Mutations in KCTD1 cause scalp-ear-nipple syndrome

Alexander G. Marneros, Anita E. Beck, Emily H. Turner, Margaret J. McMillin, Matthew J. Edwards, Michael Field, Nara Lygia De Macena Sobreira, Ana Beatriz A. Perez, Jose A.R. Fortes, Anne K. Lampe, Maria Luisa Giovannucci Uzielli, Christopher T. Gordon, Ghislaine Plessis, Martine Le Merrer, Jeanne Amiel, Ernst Reichenberger, Kathryn M. Shively, Felecia Cerrato, Brian I. Labow, Holly K. TaborJoshua D. Smith, Jay Shendure, Deborah A. Nickerson, Michael J. Bamshad

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)621-626
Number of pages6
JournalAmerican journal of human genetics
Volume92
Issue number4
DOIs
StatePublished - Apr 4 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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