TY - JOUR
T1 - Mutations in KCTD1 cause scalp-ear-nipple syndrome
AU - Marneros, Alexander G.
AU - Beck, Anita E.
AU - Turner, Emily H.
AU - McMillin, Margaret J.
AU - Edwards, Matthew J.
AU - Field, Michael
AU - De Macena Sobreira, Nara Lygia
AU - Perez, Ana Beatriz A.
AU - Fortes, Jose A.R.
AU - Lampe, Anne K.
AU - Giovannucci Uzielli, Maria Luisa
AU - Gordon, Christopher T.
AU - Plessis, Ghislaine
AU - Le Merrer, Martine
AU - Amiel, Jeanne
AU - Reichenberger, Ernst
AU - Shively, Kathryn M.
AU - Cerrato, Felecia
AU - Labow, Brian I.
AU - Tabor, Holly K.
AU - Smith, Joshua D.
AU - Shendure, Jay
AU - Nickerson, Deborah A.
AU - Bamshad, Michael J.
N1 - Funding Information:
We thank the families for their participation and support; Tracy Dudding-Byth for clinical assistance; Kati Buckingham and Christa Poel for technical assistance; and Jennifer E. Below for discussion. Our work was supported in part by grants from the National Institutes of Health National Human Genome Research Institute (1U54HG006493 to M.B., D.N., and J.S.; 1RC2HG005608 to M.B., D.N., and J.S.; and 5RO1HG004316 to H.T.), the Life Sciences Discovery Fund (2065508 and 0905001), and the Washington Research Foundation.
PY - 2013/4/4
Y1 - 2013/4/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajhg.2013.03.002
DO - 10.1016/j.ajhg.2013.03.002
M3 - Article
C2 - 23541344
AN - SCOPUS:84875934480
SN - 0002-9297
VL - 92
SP - 621
EP - 626
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -