Garbes et al (2015) report a boy with turricephaly & CSS. Fetus from a second family had largely absent ossification of calvarium. ; Review on behalf of Tracy Lester and Andrew Wilkie
Created: 5 Mar 2019, 11:33 a.m.
Cole-Carpenter syndrome 2
After review with clinical experts from the GMS musculoskeletal specialist test group it was decided to keep this gene as amber based on the level of evidence for craniosynostosis.
Created: 14 Aug 2019, 1:05 p.m. | Last Modified: 14 Aug 2019, 1:05 p.m.
Panel Version: 1.124
Comment on list classification: Upgrading to Amber as there are 3 potentially relevant cases associated with variants in SEC24D. Waiting for the GMS musculoskeletal specialist test group to confirm whether all cases are relevant and it should be upgraded to green or not.
Created: 21 May 2019, 12:52 p.m.
Associated with Cole-Carpenter syndrome 2 #616294 in OMIM and probable association with SYNDROMIC OSTEOGENESIS IMPERFECTA in Gene2Phenotype.
PMID: 25683121 - Garbes et al 2015 - 7 year old boy with a syndromic form of OI that clinically classified as Cole-Carpenter syndrome, based on the history of multiple pre- and postnatal fractures and the presence of distinct craniofacial malformations. Compound heterozygosity for a SEC24D nonsense mutation (c.613C>T [p.Gln205*]) and for a missense mutation (c.3044C>T [p.Ser1015Phe]). The medaka mutant vbi, caused by a sec24d nonsense mutation, is characterized by short body length, OI, and craniofacial malformations—including an impaired ossification of the neurocranium (note, Sec24d-null mice are embryonic lethal prior to skeletal development). Fetuses with suspected to be affected by a severe type of OI from second family are likely compound heterozygous for SEC24D mutations c.3044C>T (p.Ser1015Phe) and c.2933A>C (p.Gln978Pro).
PMID: 30462379 - Takeyari et al 2018 - Japanese boy with syndromic OI. His features include a short trunk, and craniofacial abnormalities including ocular proptosis, marked frontal bossing, midface hypoplasia, and micrognathia. He had wide open fontanelle. Wormian bones, lordosis, and long thin bones were observed by skeletal imaging. He was compound heterogzyous for 2 variants in the SEC24D gene (NM_014822:c.1450C>T:p.Arg484* and c.938G>A:p.Arg313His) .
PMID: 27942778 - Zhang et al 2017 - 2 unrelated families with individuals with osteogenesis imperfecta. Compound heterozygous variants in SEC24D were found in both. Family 1 - c.2723G>A (p. Cys908Tyr) and c.2842T>C (p. Ser948Pro). Family 2 - c.938G>A (p. Arg313His) and c.875C>T (p. Pro292Leu). Proband from family 1 showed skull deformities associated with a broad frontoapical ossification defect, a widened sagittal suture, and Wormian bones. In the proband from family 2 the anterior fontanel was not closed, and he did not have obvious facial dysmorphism.
Consulting with the Genomics England Team with respect to the relevance to craniosynostosis of these phenotypes.
Created: 14 May 2019, 3:18 p.m.
Comment on publications: PMID: 25683121 - Garbes et al (2015)
Created: 14 May 2019, 1:25 p.m.
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: SEC24D; Suggested initial gene rating: amber
Created: 5 Mar 2019, 11:21 a.m.
Phenotypes for gene: SEC24D were changed from Cole-Carpenter syndrome 2 to Cole-Carpenter syndrome 2 616294
Publications for gene: SEC24D were set to 25683121
Mode of inheritance for gene: SEC24D was changed from to BIALLELIC, autosomal or pseudoautosomal
Gene: sec24d has been classified as Amber List (Moderate Evidence).
Publications for gene: SEC24D were set to
Added phenotypes Cole-Carpenter syndrome 2 for gene: SEC24D
gene: SEC24D was added gene: SEC24D was added to Craniosynostosis. Sources: NHS GMS Mode of inheritance for gene: SEC24D was set to