Details

Autor(en) / Beteiligte

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

Titel

Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome

Ist Teil von

• American journal of human genetics, 2013-04, Vol.92 (4), p.621-626

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.