Skeletal dysplasiaGene: THPO
Limb hypoplasia-reduction defects gp of SD - ?secondary to blood disorder.; Review on behalf of Tracy Lester/Michael Oldridge
Created: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Thrombocythemia 1 187950 (rare presentation with congenital limb defects)
Comment on list classification: Demoted from Green to red. Only two cases reported with a limb defect and no clear wider skeletal phenotype.
Created: 20 Nov 2019, 12:15 p.m. | Last Modified: 20 Nov 2019, 12:15 p.m.
Panel Version: 1.218
Associated with Thrombocythemia 1 #187950 (AD) in OMIM.
PMID: 19553636 - Graziano et al 2009 - report where the father has thrombocythemia and limb defects (absence of forearm and hand, absence of foot). Two sons had milder lower limb defects. A G185T heterozygous mutation was detected in THPO. The grandfather was found to have the variant and had thrombocythemia but no limb defect.
PMID: 22453305 - Stockklausner et al 2012 - report two families with Hereditary thrombocythemia resulting from a THPO c.13+1 G>C mutation in the splice donor of intron 3. In one family there were coexisting distal limb defects in 2 out of 4 individuals with thrombocythemia (complex limb defects of the left hand in one individual, and absent proximal, middle, and distal phalanges at digits 3–5, a dysplastic proximal phalanx at digit 2 with absent middle and distal phalanx and shortened metacarpal bones at digits 3 and 4, carpal bones were partly fused to metacarpal bones at digits 2–5 in the other).
Created: 20 Nov 2019, 12:13 p.m. | Last Modified: 20 Nov 2019, 12:13 p.m.
Panel Version: 1.217
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: THPO; Initial rating suggestion: red
Created: 6 Mar 2019, 11:37 a.m.
Comment when marking as ready: At least two reports of variants associated with Thrombocythemia 1 187950 with congenital limb defects
Created: 12 Jul 2016, 1:56 p.m.
Comment on mode of pathogenicity: Gain of function
Created: 12 Jul 2016, 1:55 p.m.
Created: 17 Jun 2016, 8:09 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Thrombocythemia 1 187950; Stockklausner C et al. Hereditary thrombocythemia caused by a thrombopoietin (THPO) gain-of-function mutation associated with multiple myeloma and congenital limb defects. Ann Hematol. 2012 Jul, 91(7):1129-33; Graziano C et al. Association of hereditary thrombocythemia and distal limb defects with a thrombopoietin gene mutation. Blood. 2009 Aug 20, 114(8):1655-7
Variants in this GENE are reported as part of current diagnostic practice
Gene: thpo has been classified as Red List (Low Evidence).
Added phenotypes Thrombocythemia 1 187950 (rare presentation with congenital limb defects) for gene: THPO Publications for gene THPO were changed from 22453305; 19553636 to 19553636; 22453305
Source NHS GMS was added to THPO. Rating Changed from Green List (high evidence) to Green List (high evidence)
Promoted to version 1 9th August 2016
This gene has been classified as Green List (High Evidence).
Mode of pathogenicity for THPO was changed to Other - please provide details in the comments
Phenotypes for THPO were set to Thrombocythemia 1 187950 (rare presentation with congenital limb defects)
Mode of inheritance for THPO was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
THPO was added to Unexplained skeletal dysplasiapanel. Sources: Emory Genetics Laboratory,Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN
Publications for THPO were set to 22453305; 19553636
Publications for THPO were set to 22453305;
THPO was added to Unexplained skeletal dysplasiapanel. Sources:
THPO was created by sleigh