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Skeletal dysplasia v8.20 PTBP1 Arina Puzriakova edited their review of gene: PTBP1: Changed rating: GREEN; Changed publications to: 40965981; Changed phenotypes to: Neurodevelopmental disorder, MONDO:0700092; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v8.20 PTBP1 Arina Puzriakova Classified gene: PTBP1 as Amber List (moderate evidence)
Skeletal dysplasia v8.20 PTBP1 Arina Puzriakova Added comment: 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.
Skeletal dysplasia v8.20 PTBP1 Arina Puzriakova Gene: ptbp1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v8.19 PTBP1 Arina Puzriakova Phenotypes for gene: PTBP1 were changed from to Neurodevelopmental disorder, MONDO:0700092
Skeletal dysplasia v8.18 PTBP1 Arina Puzriakova Publications for gene: PTBP1 were set to PMID:40965981
Skeletal dysplasia v8.17 PTBP1 Arina Puzriakova Tag Q3_25_promote_green tag was added to gene: PTBP1.
Tag Q3_25_NHS_review tag was added to gene: PTBP1.
Skeletal dysplasia v8.17 PTBP1 Ronnie Wright gene: PTBP1 was added
gene: PTBP1 was added to Skeletal dysplasia. Sources: NHS GMS,Literature
Mode of inheritance for gene: PTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTBP1 were set to PMID:40965981
Penetrance for gene: PTBP1 were set to unknown
Review for gene: PTBP1 was set to GREEN
Added comment: 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