Transcatheter Tricuspid Valve Replacement: When do Signals Become Evidence?

Q: What is the clinical evidence from this study?

Study design: Case Report. Population: early-onset rickets (n=2). Intervention: CYP3A4 c.902T>C (p.I301T) mutation vs. WT CYP3A4. Primary outcome: 1,25-dihydroxyvitamin D oxidation activity in vitro (10-fold greater activity).

Q: What does this research mean for the field?

A recurrent de novo missense mutation in CYP3A4 (c.902T>C) causes early-onset rickets through accelerated enzymatic inactivation of vitamin D metabolites. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

Domenico Angellotti; Fabien Praz

doi:10.48620/98680

June 12, 2026Open Access

Transcatheter Tricuspid Valve Replacement: When do Signals Become Evidence?

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Study Design

Type

Case Report (n=2)

Structured PICO

P

Population

Two unrelated patients with early-onset rickets, reduced vitamin D metabolites, and deficient responsiveness to vitamin D.

E

Exposure

Whole exome sequencing analysis and in vitro functional testing

C

Comparator

Wild-type CYP3A4 and CYP24A1 (for in vitro assays)

O

Outcome

Identification of genetic mutation causing the phenotype and its in vitro enzymatic activitysurrogate

Main Result

Effect estimate: 10-fold greater activity

Implication

Accelerated inactivation of vitamin D metabolites by a CYP3A4 mutation represents a novel mechanism for vitamin D deficiency and early-onset rickets.

Discussion

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Cite This Study

Angellotti et al. (2026) conducted a case report in early-onset rickets (n=2). CYP3A4 c.902T>C (p.I301T) mutation vs. WT CYP3A4 was evaluated on 1,25-dihydroxyvitamin D oxidation activity in vitro (10-fold greater activity).

synapsesocial.com/papers/6a3263fe8b0a6d04ea8e6a4c https://doi.org/10.48620/98680

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Transcatheter Tricuspid Valve Replacement: When do Signals Become Evidence?

Study Design

Structured PICO

Main Result

Implication

Discussion

Cite This Study

Transcatheter Tricuspid Valve Replacement: When do Signals Become Evidence?

Study Design

Structured PICO

Main Result

Implication

Discussion

Cite This Study

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