Skeletal dysplasiaGene: SLCO5A1
Mesomelic and rhizo-mesomelic dysplasias gp of SD - >3 cases reported. Robinow-like phenotype. 8q13 microdel inc SULF1; Review on behalf of Tracy Lester
Created: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mesomelia-synostoses syndrome 600383
Mode of pathogenicity
Other - please provide details in the comments
Comment on list classification: Changing rating back to red. In all reported cases associated with deletions and patients with Mesomelia-synostoses syndrome both SULF1 and SLCO5A1 are deleted, so better to represent this as a region
Created: 21 Nov 2019, 10:44 p.m. | Last Modified: 21 Nov 2019, 10:44 p.m.
Panel Version: 1.244
Comment on list classification: Changing rating to green. Deletions covering this gene will be reported.
Created: 21 Nov 2019, 4:43 p.m. | Last Modified: 21 Nov 2019, 4:43 p.m.
Panel Version: 1.239
Not associated with any phenotype in OMIM or Gene2Phenotype.
PMID: 20602915 - Isidor et al 2010 - using whole-genome oligonucleotide array CGH, they identified an interstitial deletion at 8q13 in 5 patients from 4 unrelated families with Mesomelia-synostoses syndrome. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1 and SLCO5A1. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Codeletion of SULF1 and SLCO5A1was found in all patients, suggesting that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS.
PMID: 28328141 - Kohmoto et al 2017 - report the first Japanese case with MSS diagnosed by detecting an 8q13 deletion (581 Kb monoallelic deletion) that resulted from a unique, distant L1s‐mediated unequal NAHR event, which is different from the possible mechanisms proposed in previously reported cases. The deletion encompasses SULF1, SLCO5A1, and LINC01603. The size of the 8q13 deletion was different from those of any of the four reported deletions responsible for MSS (Isidor et al., 2010). The deletion could not be confirmed as de novo because of the unavailability of parental DNA.
PMID: 30450550 - Dardis et al 2019 - describe the first patient affected by MSS without the previously described 8q13 deletions. Patient is an 8‐year‐old 46,XY male presenting the radiological and clinical hallmarks of MSS. Microdeletions of SULF1 and SLCO5A1 genes at 8q13 were absent. Sequencing of SULF1 and SLCO5A1 found 4 polymorphisms but no pathogenic mutations. However, it was found that there was monoallelic expression of SULF1 in the patient's cells, likely leading to SULF1 haploinsufficiency. There may be either a deletion of a portion of SULF1 gene not detectable by PCR or CGH array or mutations or epigenetic alterations in sequences that contribute to the regulation of SULF1 expression.
Summary, there are 5 cases where deletions covering both SULF1 and SLCO5A1 are found in patients with MSS. There is one case of MSS in a patient with no detectable deletions of SULF1 and SLCO5A1, but with monoallelic expression of SULF1. There is no current regions curated by ClinGen that cover these genes.
Created: 20 Nov 2019, 3:51 p.m. | Last Modified: 20 Nov 2019, 3:51 p.m.
Panel Version: 1.220
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: SLCO5A1; Initial rating suggestion: green for CNVs, red for SNVs
Created: 6 Mar 2019, 11:37 a.m.
Comment when marking as ready: Four deletions ranging from 582 Kb to 738 Kb encompassing SULF1 & SLCO5A1 genes
Created: 12 Jul 2016, 1:22 p.m.
Mode of inheritance
Isidor B et al. Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13.Am J Hum Genet. 2010 Jul 9, 87(1):95-100.
Variants in this GENE are reported as part of current diagnostic practice
Gene: slco5a1 has been classified as Red List (Low Evidence).
Tag currently-ngs-unreportable was removed from gene: SLCO5A1.
Gene: slco5a1 has been classified as Green List (High Evidence).
Tag deletions tag was added to gene: SLCO5A1. Tag currently-ngs-unreportable tag was added to gene: SLCO5A1.
Added phenotypes Mesomelia-synostoses syndrome 600383 for gene: SLCO5A1
Source NHS GMS was added to SLCO5A1.
Promoted to version 1 9th August 2016
Phenotypes for SLCO5A1 were set to Mesomelia-synostoses syndrome 600383
This gene has been classified as Red List (Low Evidence).
Publications for SLCO5A1 were set to 20602915
Mode of inheritance for SLCO5A1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
SLCO5A1 was added to Unexplained skeletal dysplasiapanel. Sources: Expert list
SLCO5A1 was added to Unexplained skeletal dysplasiapanel. Sources:
SLCO5A1 was created by sleigh