Skeletal dysplasia

Gene: B9D1

Red List (low evidence)

Neither gene nor 614209 listed in SD nosology paper. Single report in OMIM of a fetus with shortened limbs and polydactyly - also had a variant in CEP290. Association unclear. Romani et al 2014 report 2 individuals with mild Joubert phenotype (no polydactyly or orofacial/skeletal features). Association with SD still unclear.; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Meckel syndrome 9 614209

Publications

• 24886560
• 21493627

I don't know

Comment on list classification: Demoting from Green to Amber, as the association with a skeletal phenotype is not clear.

Created: 17 Jul 2019, 1:30 p.m. | Last Modified: 17 Jul 2019, 1:30 p.m.

Panel Version: 1.189

Associated with ?Meckel syndrome 9 (#614209) and Joubert syndrome 27 (#617120) in OMIM.
Gene2Phenotype reports a probable association with MECKEL SYNDROME 9.

PMID: 24886560 - Romani et al 2014 - report mutations in B9D1 in two unrelated patients, a 9-year-old boy (COR363) and a 7-year-old girl (COR346), both presenting with pure JS. The mutations (cG467A; p.R156Q homo, and cA95G; p.Y32C, c.520-522delGTG; p.V175del) were inherited from heterozygous healthy parents, were not reported in public databases, and affected highly conserved residues. Missense mutations were predicted as pathogenic by prediction web tools. Neither patient showed polydactyly or orofacial features although patient COR363's facial dysmorphisms included a triangular face, retrognatism, accentuated philtrum and big ears, and patient COR346's dysmorphic facial features included frontal bossing, macrostomia, thick lips and low-set ears.

PMID: 21493627 - Hopp et al 2011 - In family M456 with Meckel syndrome (MKS), a splice-donor site change in B9D1 was detected in a fetus (c.505+2T>C). Sanger sequencing revealed likely hemizygosity of this variant, with a de novo deletion of the B9D1 locus in the fetus. The deletion spans 1.713 Mb at chromosome 17p11.2, including the complete B9D1 locus. Additionally, 18 other genes were deleted. The authors also identified a novel change in a second MKS gene, CEP290. Sanger sequencing showed that the heterozygous variant, p.R2210C, was inherited from the mother.
Polydactyly, that is typical in MKS, was not noted but the fetus had bilateral club feet and shortened limbs.

Created: 15 Jul 2019, 9:55 p.m. | Last Modified: 31 Jul 2019, 1:01 p.m.

Panel Version: 1.192

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: B9D1; Initial rating suggestion: red

Created: 6 Mar 2019, 11:36 a.m.

Comment when marking as ready: Associated with phenotype in OMIM and G2P. At least five variants reported

Created: 27 Jul 2016, 1:40 p.m.

Green List (high evidence)

Tier 2

Created: 17 Jun 2016, 8:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Meckel syndrome 9 614209

Variants in this GENE are reported as part of current diagnostic practice