Skeletal dysplasia
Gene: PAM16
Severe spondylodysplastic dysplasias gp of SD - at least 3 cases. Gene previously called MAGMAS; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type 613320
Publications
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: greenCreated: 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 reportedCreated: 29 Jul 2016, 11:39 a.m.
Comment on list classification: Two variants reported for this phenotypeCreated: 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.
Tier 1Created: 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
Gene: pam16 has been classified as Amber List (Moderate Evidence).
Added phenotypes Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type 613320 for gene: PAM16 Publications for gene PAM16 were changed from 27354339; 24786642 to 24786642; 27354339
Source NHS GMS was added to PAM16.
Promoted to version 1 9th August 2016
This gene has been classified as Red List (Low Evidence).
PAM16 was added to Unexplained skeletal dysplasiapanel. Sources: Expert list
This gene has been classified as Red List (Low Evidence).
Publications for PAM16 were set to 27354339; 24786642
Mode of inheritance for PAM16 was changed to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
PAM16 was added to Unexplained skeletal dysplasiapanel. Sources:
PAM16 was created by sleigh