Related Experiment Video

Updated: Jan 15, 2026

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

10.3K

Biallelic Variants in TMEM17 Cause Meckel-Gruber Syndrome Within the Ciliopathy Spectrum

Luba M Pardo1, Javier Martini1, Emir Zonic1

  • 1CENTOGENE GmbH, Rostock, Germany.

Clinical Genetics
|October 7, 2025
PubMed

Insights

Biallelic variants in TMEM17 cause severe Meckel-Gruber syndrome (MGS) and other primary ciliopathies. This study upgrades the TMEM17 gene-disease association, expanding the known phenotype spectrum and suggesting genotype-phenotype correlations.

Area of Science:

  • Genetics
  • Molecular Biology
  • Developmental Biology

Background:

  • TMEM17 is crucial for ciliary function, with prior reports linking homozygous variants to Joubert and Oral-Facial-Digital syndromes.
  • The role of TMEM17 variants in other primary ciliopathies, particularly severe forms, requires further investigation.

Purpose of the Study:

  • To determine if biallelic TMEM17 variants contribute to primary ciliopathies.
  • To evaluate the gene-disease relationship (GDR) for TMEM17 based on ClinGen recommendations.

Main Methods:

  • Queried a Biodatabank to identify patients with potential TMEM17-related ciliopathies.
  • Evaluated identified cases for novel homozygous TMEM17 variants and associated phenotypes.
  • Assessed the gene-disease relationship using established clinical guidelines.

Main Results:

  • Identified four unrelated families with Meckel-Gruber syndrome (MGS) and novel homozygous TMEM17 variants (c.4del, c.366dup, c.368C>G).
  • A fifth family presented with MGS phenotype in three fetuses, with parents as heterozygote carriers of c.4del.
  • Phenotypes included severe prenatal manifestations like encephalocele, polycystic kidney dysplasia, and polydactyly, leading to early lethality.

Conclusions:

  • Strengthened the TMEM17 gene-disease association from 'limited' to 'moderate'.
  • Expanded the phenotypic spectrum of TMEM17 ciliopathies to include MGS with prenatal onset and early lethality.
  • Loss-of-function TMEM17 variants are implicated in severe ciliopathies, suggesting a genotype-phenotype correlation.
Keywords:
TMEM17Meckel–Gruber syndrome (MGS)gene‐disease relationshipprimary ciliopathies

More Related Videos

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

14.2K
A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants06:35

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants

Published on: October 10, 2022

2.3K

Related Concept Videos

Microtubules in Signaling01:22

Microtubules in Signaling

The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
2.1K
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.2K
Incomplete Dominance01:43

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
29.6K
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
3.9K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.4K
Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
155.3K