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Title: | Bi-allelic SMO variants in hypothalamic hamartoma: a recessive cause of Pallister-Hall syndrome. | Austin Authors: | Green, Timothy E;Schimmel, Mareike;Schubert, Susanna;Lemke, Johannes R;Bennett, Mark F ;Hildebrand, Michael S ;Berkovic, Samuel F | Affiliation: | Epilepsy Research Centre Department of Medical Biology, University of Melbourne, Melbourne, Vic, Australia Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic, Australia Neuroscience Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Vic, Australia Children's Hospital, University Hospital Augsburg, Augsburg, Germany Institute of Human Genetics, University of Leipzig Medical Centre, Leipzig, Germany |
Issue Date: | Mar-2022 | Date: | 2022-01-16 | Publication information: | European Journal of Human Genetics 2022; 30(3): 384-388 | Abstract: | Pallister-Hall syndrome, typically caused by germline or de novo variants within the GLI3 gene, has key features of hypothalamic hamartoma and polydactyly. Recently, a few similar cases have been described with bi-allelic SMO variants. We describe two siblings born to non-consanguineous unaffected parents presenting with hypothalamic hamartoma, post-axial polydactyly, microcephaly amongst other developmental anomalies. Previous clinical diagnostic exome analysis had excluded a pathogenic variant in GLI3. We performed exome sequencing re-analysis and identified bi-allelic SMO variants including a missense and synonymous variant in both affected siblings. We functionally characterised this synonymous variant showing it induces exon 8 skipping within the SMO transcript. Our results confirm bi-allelic SMO variants as an uncommon cause of Pallister-Hall syndrome and describe a novel exon-skipping mechanism, expanding the molecular architecture of this new clinico-molecular disorder. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/30119 | DOI: | 10.1038/s41431-021-01023-4 | ORCID: | 0000-0002-4435-6610 0000-0003-2739-0515 0000-0003-4580-841X 0000-0002-6748-9651 0000-0002-3561-6804 |
Journal: | European Journal of Human Genetics : EJHG | PubMed URL: | 35034092 | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/35034092/ | Type: | Journal Article |
Appears in Collections: | Journal articles |
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