Skeletal dysplasia

Gene: PTBP1

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 11:31 p.m. | Last Modified: 11 Mar 2026, 11:31 p.m.

Panel Version: 8.37

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update based on 27 individuals from 25 families identified in PMID: 40965981 with start-loss (89%) or missense (11%) variants, confirmed de novo in 23/27 (plus 2 sibs with variant inherited from symptomatic mother, and segregation data unavailable in 2 others).

Skeletal anomalies were seen in 24 (89%), with the most prominent abnormalities comprising shortening and dysplasia of long bones and phalanges. Radiographic features included brachymetacarpia, brachymetatarsia, brachydactyly, brachytelephalangy, brachymesophalangy, and rhizomelia. Advanced bone maturation, cone-shaped epiphyses, and other features such as vertebral dysplasia were also observed.

Created: 21 Oct 2025, 10:05 a.m. | Last Modified: 21 Oct 2025, 10:05 a.m.

Panel Version: 8.20

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder, MONDO:0700092

Publications

• 40965981

Green List (high evidence)

One publication (PMID: 40965981). 27 individuals from 25 families, predominantly with start loss variants (recurring de novo).

'Affected individuals presented with a syndromic neurodevelopmental disorder and variable skeletal dysplasia with disproportionate short-limbed short stature. Intellectual functioning ranged from normal to moderately delayed'
'Additional clinical features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%)'

For the start loss variants, re-initiation of translation at p.Met31 is shown to be occurring by authors, and leads to reduced nuclear localization, enhanced cytoplasmic retention and increased protein stability.

Authors showed a recognizable methylation episignature.

Cases in CVA (incl 1 North West GLH), at least some of which share syndromic phenotypic features consistent with the literature report.
Sources: NHS GMS, Literature

Created: 14 Oct 2025, 1:01 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• PMID:40965981