Bi-allelic SMO variants in hypothalamic hamartoma: a recessive cause of Pallister-Hall syndrome
- Author(s)
- Green, TE; Schimmel, M; Schubert, S; Lemke, JR; Bennett, MF; Hildebrand, MS; Berkovic, SF;
- Journal Title
- European Journal of Human Genetics
- Publication Type
- epub ahead of print
- 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.
- Publisher
- NPG
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 35034092
- Publisher's Version
- https://doi.org/10.1038/s41431-021-01023-4
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-02-18 11:34:22
Last Modified: 2022-02-18 03:12:15