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Skeletal dysplasia

Gene: MBTPS1

Amber List (moderate evidence)

MBTPS1 (membrane bound transcription factor peptidase, site 1)
EnsemblGeneIds (GRCh38): ENSG00000140943
EnsemblGeneIds (GRCh37): ENSG00000140943
OMIM: 603355, Gene2Phenotype
MBTPS1 is in 1 panel

2 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting this gene from grey to amber, but with recommendation of green rating following GMS review. 3 independent cases reported with biallelic variants in this gene and a skeletal phenotype.
Created: 20 Jan 2021, 10:26 p.m. | Last Modified: 20 Jan 2021, 10:26 p.m.
Panel Version: 2.65
Provisionally associated with ?Spondyloepiphyseal dysplasia, Kondo-Fu type#618392 (AR) in OMIM.

PMID:32857899 - Meyer et al 2020 - report a 7 year old boy diagnosed with Silver–Russell syndrome. Using WES a homozygous variants in MBTPS1 was identified, c.1094A>G, p.Asp365Gly, which had already been reported in the patient of Kondo et al. The patient's clinical phenotype included funnel chest, kyphosis, (slight) pes valgus and sandal grooves, unilateral inguinal hernia, bilateral anterior and posterior subcapsular cataract, macrocephaly, growth retardation.

PMID:32420688 - Carvalho et al 2020 - report a 5‐year‐old Brazilian girl from a consanguineous couple. The child presented short stature with rhizomelic limb shortening and severe retromicrognathia. Congenital lamellar cataract, seizures and developmental delay are also noted. 6 lysosomal enzymes had increased activities in plasma, but had normal activity in leukocytes. WES on the pobands and parents identified a homozygous variant in MBTPS1 (c.2948G>A: p.Trp983ter) . Each parent was heterozygous for this variant.

PMID:30046013 - Kondo et al 2018 - report a child with skeletal dysplasia and elevated blood lysosomal enzymes. Using WES, they identified compound heterozygous variants in MBTPS1 (c.285dupT, p.D96X from father, and c.1094A>G, p.D365G from mother). The patient had approx 1% of the expected functional MBTPS1 transcripts. The patient's main clinical phenotypes are retarded growth with skeletal abnormalities, including a bone mineral density of approximately 60% relative to healthy controls. She also had elevated plasma levels of lysosomal enzymes compared to her parents and a healthy control.

Monoallelic cases
PMID: 31070020 - Schweitzer et al 2019 describe a female patient with a heterozygous missense mutation in MBTPS1, but the phenotype was not skeletal but instead was episodic, activity-induced, focal myoedema and myalgias with hyperCKemia. She also had gastrointestinal hypomotility, ocular migraines, and polycystic ovary syndrome.
Created: 20 Jan 2021, 10:25 p.m. | Last Modified: 20 Jan 2021, 10:25 p.m.
Panel Version: 2.64

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Spondyloepiphyseal dysplasia, Kondo-Fu type OMIM:618392; spondyloepiphyseal dysplasia, kondo-fu type MONDO:0032721

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature.
Sources: Literature
Created: 5 Oct 2020, 9:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Skeletal dysplasia

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Skeletal dysplasia
  • ?Spondyloepiphyseal dysplasia, Kondo-Fu type OMIM:618392
  • spondyloepiphyseal dysplasia, kondo-fu type MONDO:0032721
Tags
for-review
OMIM
603355
Clinvar variants
Variants in MBTPS1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 Jan 2021, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: MBTPS1.

20 Jan 2021, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: MBTPS1 were changed from Skeletal dysplasia to Skeletal dysplasia; ?Spondyloepiphyseal dysplasia, Kondo-Fu type OMIM:618392; spondyloepiphyseal dysplasia, kondo-fu type MONDO:0032721

20 Jan 2021, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013

20 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: mbtps1 has been classified as Amber List (Moderate Evidence).

5 Oct 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: MBTPS1 was added gene: MBTPS1 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013 Phenotypes for gene: MBTPS1 were set to Skeletal dysplasia Review for gene: MBTPS1 was set to GREEN gene: MBTPS1 was marked as current diagnostic