Osteogenesis Imperfecta and Osteoporosis

Gene: P3H1

Green List (high evidence)

11 new patients from seven related families from the Karen population affected with OI type VIII. chr1:43212857A > G variant suspected to be founder effect from Karen ancestry.

Suggestion that isoform a is the functional isoform that can modify the collagen precursor protein in the endoplasmic reticulum.

Homozygous P3H1 (chr1:43212857A > G; NM_001243246.1; c.2141A > G) variants in coding region of isoform c.
The same variant P3H1 (chr1:43212857A > G; NM_022356.4:c.2055 + 86A > G) lies in non-coding region of isoform a. Splice site prediction algorithm ASSP suggests this variant creates a new “CAG” splice acceptor sequence, which is predicted to result in an alternative, novel C-terminal sequence and premature protein truncation.

All 11 patients had similar radiology appearance: generalised osteopenia, short thorax, platyspondyly, slender ribs, rhizomelia, slender curved long bones, multiple fractures. Metaphyses bulbous, flared, and irregularly ossified ('pop corn calcifications'). Phalanges appeared long. No patient had blue sclera.

Created: 29 Apr 2024, noon | Last Modified: 29 Apr 2024, noon

Panel Version: 0.113

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Osteopenia HP:0000938; Platyspondyly HP:0000926; MONDO:0012581

Publications

• PMID: 36833249

Mode of pathogenicity
Other

Green List (high evidence)

PMID: 17277775; 5 families including functional studies of c.1080+1G>T, which results in 5 alternatively spliced isoforms
PMID: 18566967; 16 probands

Created: 18 May 2020, 6:20 a.m. | Last Modified: 18 May 2020, 6:20 a.m.

Panel Version: 0.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Osteogenesis imperfecta, type VIII, (MIM# 610915)

Publications

• PMID: 17277775
• 18566967