Bi-allelic variants in TM2D3 cause a severe syndromic neurodevelopmental disorder associated with endoplasmic reticulum and mitochondrial abnormalities.

doi:10.1016/j.ajhg.2025.05.004

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Article

Bi-allelic variants in TM2D3 cause a severe syndromic neurodevelopmental disorder associated with endoplasmic reticulum and mitochondrial abnormalities.

American journal of human genetics - 3 Jul 2025

Gabillard-Lefort Claudie, Martinez Caroline Silveira, Gueguen Naïg, Desquiret-Dumas Valérie, Wery Méline, Legoff Louis, Guimier Anne, Rondeau Sophie, Barcia Giulia, Barnerias Christine, Cogne Benjamin, Besnard Thomas, Lorino Elsa, Douglas Jessica, Bodamer Olaf, Vetro Annalisa, Guerrini Renzo, Balestrini Simona, Conti Valerio, Siri Laura, Chevrollier Arnaud, Bris Céline, Colin Estelle, Procaccio Vincent, Prunier-Mirebeau Delphine, Lenaers Guy, Khiati Salim, Nizon Mathilde, Baris Olivier R

Abstract excerpt

We identified via exome sequencing bi-allelic variants in TM2D3 in four affected individuals from four unrelated families with overlapping clinical presentations, including microcephaly, severe global developmental delay with absent speech, autistic features, heart malformation, and dysmorphic facial features. TM2D3 encodes a transmembrane protein present in many tissues, with a higher abundance in the central...

Topics

Humans
Endoplasmic Reticulum
Mitochondria
Male
Neurodevelopmental Disorders
Female
Alleles

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Endoplasmic Reticulum Chaperone BiP

Membrane Proteins

Child, Preschool

Fibroblasts

Pedigree

Child

Endoplasmic Reticulum Stress

Infant

Exome Sequencing

Source

Open in PubMed Open full text

Identifiers

PMID: 40449487
DOI: 10.1016/j.ajhg.2025.05.004
PMCID: PMC12256896

Genes

TM2D3
ATF4
DDIT3
HSPA5

Variants

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 31 Aug 2026.

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