1. Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance
- Author
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Ingrid M. Wentzensen, R. Colombo, L. Baker, L. Immken, T. Barbaro-Dieber, Cameron Mroske, Julie S. Cohen, H. Nagakura, Ali Fatemi, J.F. Reynolds, E.S. Jordan, Zöe Powis, Christopher Cunniff, M. T. Cho, Jennifer Burton, Kirsty McWalter, I. Petrik, Rebecca Willaert, Kevin R. Payne, Joseph H. Hersh, Robert Huether, K.A. Aleck, Karen W. Gripp, T. Stamper, K.D. Farwell Hagman, M.J. Guillen Sacoto, K.L. David, Alessandro Serretti, Sha Tang, Powis, Z., Farwell Hagman, K.D., Mroske, C., McWalter, K., Cohen, J.S., Colombo, R., Serretti, A., Fatemi, A., David, K.L., Reynolds, J., Immken, L., Nagakura, H., Cunniff, C.M., Payne, K., Barbaro-Dieber, T., Gripp, K.W., Baker, L., Stamper, T., Aleck, K.A., Jordan, E.S., Hersh, J.H., Burton, J., Wentzensen, I.M., Guillen Sacoto, M.J., Willaert, R., Cho, M.T., Petrik, I., Huether, R., and Tang, S.
- Subjects
Adult ,Male ,0301 basic medicine ,Adolescent ,Developmental Disabilities ,Penetrance ,Biology ,Young Adult ,03 medical and health sciences ,Genetic ,Intellectual Disability ,Exome Sequencing ,Intellectual disability ,Genetics ,medicine ,Humans ,Global developmental delay ,Child ,Gene ,Genetics (clinical) ,Exome sequencing ,Sequence (medicine) ,Infant ,SETD5 ,Methyltransferases ,Middle Aged ,Body Dysmorphic Disorders ,medicine.disease ,Phenotype ,haploinsufficiency ,030104 developmental biology ,Child, Preschool ,Mutation ,Female ,Chromosomes, Human, Pair 3 ,Chromosome Deletion ,Haploinsufficiency - Abstract
Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SET domain containing 5 gene (SETD5) phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Herein, we present additional patients with pathogenic SETD5 sequence alterations. The majority of patients in this cohort and previously reported have developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities. We also present an apparently unaffected carrier mother of an affected individual and a carrier mother with normal intelligence and affected twin sons. We suggest that the phenotype of SETD5 is more complex and variable than previously presented. Therefore, many features and presentations need to be considered when evaluating a patient for SETD5 alterations through DES.
- Published
- 2018