Discipline: Biological Sciences
Keiva Aguilera-Montero - University of Washington
Scalp-Ear-Nipple syndrome (SEN) is an autosomal-dominant disorder characterized by the following features: cutis aplasia, anomalies of the external ear and malformation or absence of the breast or nipple. Previous cases have been reported to be caused by mutations in the coding exons 2 and 3 in the gene potassium channel tertramerization domain containing 1, KCTD1 (Marneros et al., 2013). Recently a family with affected individuals have been described to have characteristics typical of the phenotype of SEN, thus the aim of this research is to screen this pedigree for mutations in the gene KCTD1. This research will help to further the limited information about SEN farther and give great assistance to the family by explaining their phenotype as a genetic cause. Each individual of the pedigree is analyzed to test the hypothesis that the affected individuals of family have a missense mutation in KCTD1 which will help determine the cause of their phenotype. Primers were used to amplify the coding exons of KCTD1 during a PCR from genomic DNA of each individual. Gel Electrophoresis was used to confirm success of PCR and band size. BDT was used for DNA sequencing reactions and electropherograms were created using an ABI 3130xl Sanger Sequencer. Each electropherogram from the pedigree was aligned to a human control reference sequence (MC1) and examined using CodonCode Aligner. The results of the research showed the affected individuals of the pedigree were mutationnegative for the coding region of KCTD1. However, upon further review of the pedigree’s phenotype, the family does have all the characteristics of SEN but share slight deviations by the addition of other characteristics. Such as the affected father and the proband have cutis aplasia but the affected sister does not, she has renal hypoplasia. The father also has excess nipples, not athelia like typical SEN traits. These results suggest future research questions, such as, whether this pedigree with their unique pedigree classify into a new subgroup of SEN or possibly have a new disorder with characteristics similar to SEN. We are interested in studying the family further to try and determine the genetic cause of their physical characteristics. As a result, the pedigree will be sent for exome sequencing to analyze their coding exons to determine the causal gene for their phenotype.
References: Marneros, Alexander G., et al. “Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome.” The American Journal of Human Genetics 92.4 (2013): 621-26.
Funder Acknowledgement(s): Thank you Kathryn Shively and the other assisting mentors, Kati Buckingham and Colby Marvin for helping with my project. Thanks to Michael Bamshad for providing the opportunity to work in the Bamshad lab. Grants used to fund my research were University of Washington GenOM project (NIH 5R25GG007153-03) and the generous donation from Dr. Anne Dinning and Dr. Michael Wolf.
Faculty Advisor: Lisa Peterson,