Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: IFT140
Comment on list classification: There is sufficient evidence (at least 3 cases) for this gene to be promoted to GREEN rating in the next GMS update.Created: 12 May 2023, 12:26 p.m. | Last Modified: 12 May 2023, 12:26 p.m.
Panel Version: 4.72
PMID:22503633 - two cases from a single family with craniosynostosis, scaphocephaly and facial dysmorphy.
PMID:27874174 - single case with trigonocephaly and additional ciliopathy-related clinical features.
PMID:28288023 - single case with evolving craniofacial phenotype, striking brachydactyly and sensenbrenner syndromeand it was not clear if craniosynostosis was radiologically confirmed (as reviewed by Rebecca Tooze).
PMID:32007091 - single case with craniosynostosis and dolichocephaly.Created: 12 May 2023, 12:25 p.m. | Last Modified: 12 May 2023, 12:25 p.m.
Panel Version: 4.71
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920
Publications
• One male patient with distinctive clinical features of Sensenbrenner syndrome (dolichocephaly, shortening of long bones and early onset renal failure, ectodermal anomalies and small teeth was found to harbour a tandem duplication variant p.(Tyr1152_Thr1394dup) on one allele and a novel missense variant, p.(Leu109Pro), on the second allele (Walczak-Sztulpa et al., 2020).
• An individual with trigonocephaly and additional ciliopathy-related clinical features was found to harbour compound heterozygous variants in the IFT140 gene: a substitution at the splice donor site of exon 24 (c.723+1G>T; p.(?)) and a 17 bp deletion, impacting the first coding exon (c.-11_6del; p.(?)). These variants were confirmed by dideoxy-sequencing (Pena-Padilla et al., 2017).
• A patient was reported with brachydactyly (it is not clear if craniosynostosis was radiologically confirmed) and Sensenbrenner syndrome. Whole exome sequencing as part of the DDD study evidenced compound heterozygosity for IFT140: c.634G>A; p.(Gly212Arg) and c.2278C>T; p.(Arg760Ter) (Bayat et al., 2017).Created: 2 Mar 2023, 1:28 p.m. | Last Modified: 2 Mar 2023, 1:28 p.m.
Panel Version: 3.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypic overlap with cranioectodermal dysplasia (IFT122 gene). Perrault et al 2012 report 2 patients from 1 family with CSS. Pena-Padilla et al 2017 report an infant with trigonocephaly. Amber/green - 3 cases but only 2 families? Added by GOSH - Bayat et al (2017) reported patient with evolving craniofacial phenotype, striking brachydactyly and sensenbrenner syndrome ; Review on behalf of Tracy Lester/Andrew Wilkie/GOSHCreated: 5 Mar 2019, 11:33 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Short-rib thoracic dysplasia with or without polydactyly; asphyxiating thoracic dysplasia (ATD,Jeune)
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 11:55 a.m. | Last Modified: 11 Oct 2023, 11:55 a.m.
Panel Version: 4.174
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: IFT140; Suggested initial gene rating: amberCreated: 5 Mar 2019, 11:21 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Tag Q2_23_promote_green was removed from gene: IFT140.
Source Expert Review Green was added to IFT140. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_23_promote_green tag was added to gene: IFT140.
Publications for gene: IFT140 were set to 27874174; 28288023; 32007091
Gene: ift140 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: IFT140 were changed from hort-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920 to Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920
Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia with or without polydactyly; asphyxiating thoracic dysplasia (ATD,Jeune) to hort-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920
Publications for gene: IFT140 were set to
Mode of inheritance for gene: IFT140 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Short-rib thoracic dysplasia with or without polydactyly; asphyxiating thoracic dysplasia (ATD,Jeune) for gene: IFT140
gene: IFT140 was added gene: IFT140 was added to Craniosynostosis. Sources: NHS GMS Mode of inheritance for gene: IFT140 was set to