Osteogenesis Imperfecta and Osteoporosis

Gene: TAPT1

I don't know

PMID: 36697720 - reports a patient with a biallelic frameshift variant in an infant with bilateral cateract, dysmorphic features, poor weight gain, and clinical symptoms reminiscent of osteogenesis imperfecta. A zebrafish knockout model showed aberrant lens development but no visible skeletal involvement.

PMID: 36652330 - identified 6 patients from 2 consanguineous families with recessive osteogenesis imperfecta (OI), severe developmental delay and neonatal progeria. All were homozygous for a deep intronic variant c.1237-52 G>A. Functional testing showed that transcription was not affected in patient fibroblasts but suggested a defect in pre-mRNA processing, resulting in an increase of TAPT1 exon 12 skipping, creating a protein-null allele, although a small amount of WT expression remained.

Rated Amber due to ? phenotype inconsistency with previous reports, and uncertainty around pathogenicity of the deep intronic variant.

Created: 1 Jun 2023, 2:25 a.m. | Last Modified: 1 Jun 2023, 2:25 a.m.

Panel Version: 0.106

Phenotypes
Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897)

Publications

• 36697720
• 36652330

Variants in this GENE are reported as part of current diagnostic practice

I don't know

2 families reported with function studies showing absent or abnormal primary cillia formation. Amber/Green pending additional reports PMID: 26365339; Reported 2 consang fam (1 splice and 1 missense) with Complex Lethal Osteochondrodysplasia. Functional studies showed abnormal ciliogenesis. Tapt1b deficient zebrafish showed decreased cilial length

Created: 4 May 2020, 11:08 a.m. | Last Modified: 4 May 2020, 11:08 a.m.

Panel Version: 0.10

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897)

Publications

• 26365339