Researchers find multisystem disorder caused by CCDC47 variants

STRASBURG, PA & TOPEKA, IN- Researchers and clinicians through a multicenter collaboration have identified a novel multisystem disorder caused by bi-allelic variants in the CCDC47 gene. Their findings are reported in the American Journal of Human Genetics. CCDC47 is responsible for encoding an essential calcium (Ca2+)-binding protein involved in embryogenesis and development. Calcium signaling is essential for various cellular processes including muscle contraction, secretion regulation, cell proliferation, and gene transcription. In this study, detailed clinical characterization and functional studies were performed on four unrelated individuals with a complex multisystem disorder characterized by woolly hair, liver dysfunction, itchy skin, unusual facial features, low muscle tone, and global developmental delay. Whole exome sequencing and family-based genomic analyses were performed at three different research centers and were used to identify the underlying genetic variants in CCDC47 associated with the condition. In this study, cells from individuals with the damaging alleles showed decreased CCDC47 gene expression and protein levels, supporting the pathogenic nature of these variants. Two of the four patients included in this study were evaluated at The Community Health Clinic in Topeka, IN by clinicians from the Clinic for Special Children and The Community Health Clinic.

The study demonstrates the important role of CCDC47 in normal development and the clinical consequence of its absence. The authors note that the identification and characterization of additional individuals will help further clarify key clinical features of this multisystem disorder, as patients demonstrated some variability in the clinical presentation of the disorder.


The research was conducted by a team including the study’s co-lead authors Marie Morimoto,1,15 Helen Waller-Evans,2,15 Zineb Ammous,3,15 Xiaofei Song,4,15 Kevin A. Strauss,5 Davut Pehlivan,4 Claudia Gonzaga-Jauregui,6 Erik G. Puffenberger,5 Charles R. Holst,7 Ender Karaca,4 Karlla W. Brigatti,5 Emily Maguire,2 Zeynep H. Coban-Akdemir,4 Akiko Amagata,7 Christopher Lau,1 Xenia Chepa-Lotrea,1 Ellen Macnamara,1 Tulay Tos,8 Sedat Isikay,9 Michele Nehrebecky,1 John D. Overton,6 Matthew Klein,7 Thomas C. Markello,1 Jennifer E. Posey,4 David R. Adams,1,10,11 Emyr Lloyd-Evans,2 James R. Lupski,4,12,13,14 William A. Gahl,1,10,11 May Christine V. Malicdan1,10,11


1National Institutes of Health Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD 20892, USA 2School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK 3The Community Health Clinic, Topeka, IN 46571, USA 4Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA 5Clinic for Special Children, Strasburg, PA 17579, USA 6Regeneron Genetics Center, Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA 7BioElectron Technology Corporation, Mountain View, CA 94043, USA 8Department of Medical Genetics, Dr. Sami Ulus Research and Training Hospital of Women’s and Children’s Health and Diseases, Ankara 06080, Turkey 9Department of Physiotherapy and Rehabilitation, Hasan Kalyoncu University, School of Health Sciences, Gaziantep 27000, Turkey 10Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 11Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 12Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA 13Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA 14Texas Children’s Hospital, Houston, TX 77030, USA 15These authors contributed equally to this work.

About the Clinic for Special Children

The Clinic for Special Children (CSC) is a non-profit organization located in Strasburg, PA, which provides primary pediatric care and advanced laboratory services to those who suffer from genetic or other complex medical disorders. Founded in 1989, the organization provides services to over 1,050 active patients and is recognized as a world-leader in translational and precision medicine. The organization is primarily supported through community fundraising events and donations. For more information, please visit

About The Community Health Clinic

The Community Health Clinic (CHC) is a non-profit organization healthcare facility located in Topeka, IN, which provides clinical genetic services to all individuals, regardless of religion, race, or age. Services include, but are not limited to, access to a clinical geneticist, physician assistant, nurse, metabolic dietician, and genetic counselor. The CHC embraces, incorporates and promotes participation in research to advance medical knowledge and improve care. For more information, please visit

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