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Title: Small interstitial 9p24.3 deletions principally involving KANK1 are likely benign copy number variants.
Austin Authors: Wallis, Mathew J ;Boys, Amber;Tassano, Elisa;Delatycki, Martin B 
Affiliation: Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Melbourne, Australia
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia
Victorian Clinical Genetics Service, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia
Clinical Genetics
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Laboratorio di Citogenetica, Istituto Giannina Gaslini, Genova, Italy
Issue Date: Jan-2020
Date: 2019-01-23
Publication information: European Journal of Medical Genetics 2020; 63(1): 103618
Abstract: A small heterozygous deletion involving KANK1 was originally reported in 2005 to cause cerebral palsy in one large Israeli family of Jewish Moroccan origin. There were nine affected children over two generations to five unaffected fathers. All of these children had congenital hypotonia that evolved into spastic quadriplegia over the first year of life, along with intellectual impairment and brain atrophy. The subsequent clinical depictions of other individuals with neurological disease harbouring a comparable KANK1 deletion have been extremely variable and most often quite dissimilar to the original family. The reported pathogenicity of these deletions has also been variable, due to an inconsistent nature of reported disease associations and limited data. We therefore sought to perform a review of the significance of small distal interstitial chromosome 9p24.3 deletions principally involving KANK1, including data from the VCGS cytogenetics laboratory. We found that carrier parents do not appear to display an increased frequency of neurological disease, individuals with a small KANK1 deletion have sometimes been found to have an alternate genetic diagnosis that explained their neurological condition, and small KANK1 deletions can be seen with approximate equal frequency in case and control populations. These data led us to conclude that small deletions involving KANK1 do not cause a highly-penetrant influence of large effect size and they are unlikely to contribute significantly to the aetiology of disease in patients with development delay, intellectual disability, autism or cerebral palsy. We recommend searching for an alternate explanation for disease in individuals with a neurological disorder found to have a small deletion involving KANK1.
DOI: 10.1016/j.ejmg.2019.01.008
Journal: European Journal of Medical Genetics
PubMed URL: 30684669
Type: Journal Article
Subjects: Autism spectrum disorder
Cerebral palsy
Chromosomal microarray
Chromosome abnormality
Developmental delay
Intellectual disability
Appears in Collections:Journal articles

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