Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome

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• 作者：Alexander G. Marneros¹ ; ¹⁸ ; Anita E. Beck² ; ¹⁸ ; Emily H. Turner³ ; ¹⁸ ; Margaret J. McMillin² ; Matthew J. Edwards⁴ ; Michael Field⁵ ; Nara Lygia de Macena Sobreira⁶ ; Ana Beatriz A. Perez⁷ ; Jose A.R. Fortes⁸ ; Anne K. Lampe⁹ ; Maria Luisa Giovannucci Uzielli¹⁰ ; ¹¹ ; Christopher T. Gordon¹² ; ¹³ ; Ghislaine Plessis¹⁴ ; Martine Le Merrer¹⁴ ; Jeanne Amiel¹⁴ ; Ernst Reichenberger¹⁵ ; Kathryn M. Shively² ; Felecia Cerrato¹⁶ ; Brian I. Labow¹⁶ ; Holly K. Tabor¹⁷ ; Joshua D. Smith³ ; Jay Shendure³ ; Deborah A. Nickerson³ ; Michael J. Bamshad² ; ³ ; ^{mbamshad@uw.edu} ; the University of Washington Center for Mendelian Genomics
• 刊名：The American Journal of Human Genetics
• 出版年：2013
• 出版时间：4 April, 2013
• 年：2013
• 卷：92
• 期：4
• 页码：621-626
• 全文大小：625 K

文摘

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-2¦Á (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.