Bi-allelic SMO variants in hypothalamic hamartoma: a recessive cause of Pallister-Hall syndrome.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
30
07
2021
accepted:
06
12
2021
revised:
21
10
2021
pubmed:
17
1
2022
medline:
3
5
2022
entrez:
16
1
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35034092
doi: 10.1038/s41431-021-01023-4
pii: 10.1038/s41431-021-01023-4
pmc: PMC8904774
doi:
Substances chimiques
SMO protein, human
0
Smoothened Receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
384-388Informations de copyright
© 2021. The Author(s), under exclusive licence to European Society of Human Genetics.
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