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| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.16 | PTCH1 |
Andrew Wilkie gene: PTCH1 was added gene: PTCH1 was added to Craniosynostosis. Sources: Expert Review Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PTCH1 were set to 31578813 Phenotypes for gene: PTCH1 were set to metopic craniosynostosis Penetrance for gene: PTCH1 were set to Incomplete Review for gene: PTCH1 was set to GREEN Added comment: Several lines of evidence support that heterozygous loss-of-function mutations in PTCH1, which cause the classical genetic disorder Gorlin (basal cell naevus) syndrome, rarely also cause metopic synostosis. It is especially important to recognise this association, given the implications for patient management from a diagnosis of Gorlin syndrome. (1) Beltrami et al (see PMID 31578813) described a frameshift variant in PTCH1 in a child with metopic synostosis. (2) At the ESHG conference 2020, Di Giovanni et al reported 2 cases of apparently isolated trigonocephaly found to have nonsense or frameshift varaints in PTCH1. The abstract is available on weblink: https://www.abstractsonline.com/pp8/#!/9102/presentation/1801. (3) Deletions of 9q22.3 including PTCH1 are well recognised to be associated with metopic synostosis (reviewed Yamada PMID:32028043), although genes additional to PTCH1 are included in the deleted region. (4) In the 100kGP, the submitter is aware of a case that was missed by GEL/GMC pipeline (found by research lab) because PTCH1 was not included in the Panel for craniosynostosis. (5) The consequence of PTCH1 loss-of-function mutations is to increase hedgehog (Hh) signalling through de-repression of Smoothened. Mutations in other genes associated with Hh overactivity, in the genes SMO, RAB23 and MEGF8, are all associated with craniosynostosis and are green panel app genes. A mice mutated in the Ptch1 orthologue, dogface-like, has lambdoid craniosynostosis (PMID:23897749). Hence, a clear biological mechanism exists accounting for craniosynostosis. Sources: Expert Review |
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| Rare syndromic craniosynostosis or isolated multisuture synostosis v1.72 | RAB23 | Eleanor Williams Added phenotypes Carpenter syndrome 201000 for gene: RAB23 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v1.47 | RAB23 | Tracy Lester reviewed gene: RAB23: Rating: GREEN; Mode of pathogenicity: ; Publications: 17503333; Phenotypes: Carpenter syndrome, 201000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v1.46 | RAB23 | Eleanor Williams reviewed gene: RAB23: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v1.45 | RAB23 |
Eleanor Williams Source NHS GMS was added to RAB23. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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