Skeletal dysplasia

Gene: PTBP1

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