Skeletal dysplasia

Gene: PAM16

Green List (high evidence)

Severe spondylodysplastic dysplasias gp of SD - at least 3 cases. Gene previously called MAGMAS; Review on behalf of Tracy Lester

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type 613320

Publications

• 27354339
• 24786642

I don't know

Comment on list classification: 3 cases, but two are likely to share the same founder mutation. Rating amber until further cases are reported.

Created: 17 Jul 2019, 1:02 p.m. | Last Modified: 17 Jul 2019, 1:02 p.m.

Panel Version: 1.183

Associated with Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type (#613320) in OMIM.

PMID: 27354339 - Moosa et al 2016 - 1 patient with distantly related Argentinian parents of central European descent, with a spondylometaphyseal dysplasia, most closely resembling odontochondrodysplasi. A homozygous c.221A>C (p.Q74P) mutation in PAM16, which was not present in the ExAC database was identified.

PMID: 24786642 - Mehawej et al 2014 - Two unrelated consanguineous Lebanese families with four affected cases presenting a novel type of early lethal spondylodysplastic dysplasia. Identified c.226A>G transition in MAGMAS (PAM16) to segregated with the disease in both families. The mutation was homozygous in the patients, heterozygous in the parents and in the unaffected sibs in both families. Likely founder mutation.
Show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein.

Created: 7 May 2019, 7:01 p.m. | Last Modified: 17 Jul 2019, 1 p.m.

Panel Version: 1.182

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: PAM16; Initial rating suggestion: green

Created: 6 Mar 2019, 11:36 a.m. | Last Modified: 17 Jul 2019, 12:53 p.m.

Panel Version: 1.182

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

Created: 29 Jul 2016, 11:39 a.m.

Comment on list classification: Two variants reported for this phenotype

Created: 11 Jul 2016, 9:12 a.m.

Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)

Created: 21 Jun 2016, 1:01 p.m.

Green List (high evidence)

Tier 1

Created: 17 Jun 2016, 8:06 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type 613320

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