Skeletal dysplasia

Gene: HNRNPK

I don't know

Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to a point mutation. Two cases - skeletal anomalies, including hip dysplasia, scoliosis, and extra lumbar vertebrae; Two cases reported: 1 had multiple vertebral segmentation defects. One patient had planovalgus feet and crowded toes, whereas the other had postaxial polydactyly and overlapping toes. ?SD, only 2 cases ; Review on behalf of Tracy Lester

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

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Au-Kline syndrome:616580; Orphanet:453499

Publications

• 26173930
• 26954065
• 26638989

I don't know

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: HNRNPK; Initial rating suggestion: Amber

Created: 6 Mar 2019, 11:36 a.m.

Comment on list classification: Source: ClinGen Gene Validity Classification Summary. Determined as MODERATE by calculated classification and MODERATE by Expert curation (dated 11/15/2016). Available here: https://search.clinicalgenome.org/kb/gene-validity/5456. Comments provided by the expert curation: Evidence is rapidly emerging supporting the association between HNRNPK and Au-Kline syndrome. Gallardo et al. published a paper in 2015 describing an Hnrnpk +/- haploinsufficient mouse, which they developed to study its role in tumorigenesis. Personal communication with the senior author of that paper, Sean Post, in August 2016, revealed that the haploinsufficient mice appeared to have "significant reduction in overall size and had numerous structural/bone abnormalities," remniscient of the human phenotype, though he clarified that his group is not able to formally assess them for these types of phenotypes. Additionally, we are aware of at least one additional unpublished case - this evidence is not being formally considered, as it is not part of the public domain.

Created: 4 Jul 2017, 2:41 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to a point mutation; OMIM:616580; Orphanet:453499

Publications

• 26173930
• 26954065
• 26638989