ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum

Frontiers in Genetics, 2021 · DOI: 10.3389/fgene.2021.616329 · Published: March 4, 2021

Simple Explanation

Hemifacial microsomia (HM) is a craniofacial congenital defect involving the ﬁrst and second branchial arch, mainly characterized by ocular, ear, maxilla-zygoma complex, mandible, and facial nerve malformation. Whole-exome sequencing of a family revealed a missense mutation in a highly conserved domain of ITPR1. ITPR1 is a calcium ion channel. The knocking down of itpr1b in zebraﬁsh could lead to a remarkable decrease in craniofacial skeleton formation.

Study Duration

Not specified

Participants

A family with autosomal dominant HM, zebra fish

Evidence Level

Level not specified, Genetic and Functional Study

Key Findings

1
A missense mutation in the ITPR1 gene was identified in a family with HM.
2
ITPR1 is expressed in the first and second branchial arches during embryonic development, suggesting its involvement in craniofacial development.
3
Knockdown of itpr1b in zebrafish resulted in decreased skeleton mass in the head, particularly in structures related to Meckel's cartilage and the palatoquadrate.

Research Summary

This study identifies a missense mutation in the ITPR1 gene in a family with hemifacial microsomia (HM). The research demonstrates that ITPR1 is involved in craniofacial development, with its expression observed in the first and second branchial arches during embryonic development. Functional analysis in zebrafish reveals that knockdown of itpr1b, the zebrafish homolog of ITPR1, leads to craniofacial skeletal defects and scoliosis.

Practical Implications

Novel Candidate Gene

ITPR1 is identified as a novel candidate gene for hemifacial microsomia, potentially aiding in future diagnostics and genetic counseling.

Understanding HM Etiology

The study contributes to understanding the genetic etiology of HM by highlighting the role of ITPR1 and the EDN-PLC-DLX5/6 signaling axis.

Potential Therapeutic Targets

Identifying ITPR1's role in craniofacial development may open avenues for future therapeutic interventions targeting the EDN-PLC-DLX5/6 pathway.

Study Limitations

1
Small number of patients involved in the study
2
Causative of HM is still under dispute
3
Future investigations in mouse models defective in IPTR1 will further reveal the roles of ITPR1

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