Meckel-Gruber Syndrome: Clinical and Molecular Genetic Profiles in Two Fetuses and Review of the Current Literature

Genet Test Mol Biomarkers. 2021 Jun;25(6):445-451. doi: 10.1089/gtmb.2020.0311. Epub 2021 Jun 4.


Background: Meckel-Gruber syndrome (MKS; OMIM No. 249000) is a rare, in utero lethal disease characterized by occipital encephalocele, polycystic kidneys, and polydactyly. Methodology and Results: In this study, two fetuses diagnosed as having MKS in the prenatal period were evaluated on the basis of ultrasonographic findings, postmortem autopsy findings, and molecular genetic analyses. Using exome sequencing analyses a novel homozygous frameshift variant (NM_015631: c.530delA, p.Lys177Argfs*47) was detected at exon 4 of TCTN3 gene in case 1, and a novel homozygous synonymous variant (NM_025114: c.180G>A, p Lys60Lys) was detected at exon 3 of CEP290 gene in case 2. Case 1 is the first reported case in the literature, which showed the typical MKS clinical feature with a novel frameshift variation in the TCTN3 gene. The variant in case 2 is the first reported synonymous variant of CEP290 gene in the literature, which has been shown to affect splicing in a functional study at the RNA level. Conclusion: TCTN3 gene variants that were rarely associated with the typical MKS phenotype and all cases with these variations have been discussed in the context of genotype-phenotype. The detection of the first synonymous variant of CEP290 gene and the demonstration of its effect on splicing by a functional study are likely to contribute to the molecular etiology of MKS.

Keywords: CEP290; Meckel–Gruber Syndrome; TCTN3; exome sequencing; novel mutation.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Antigens, Neoplasm / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Cell Cycle Proteins / genetics*
  • Ciliary Motility Disorders / diagnosis
  • Ciliary Motility Disorders / genetics*
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • Encephalocele / diagnosis
  • Encephalocele / genetics*
  • Female
  • Fetus / abnormalities*
  • Genetic Testing
  • Humans
  • Karyotyping
  • Polycystic Kidney Diseases / diagnosis
  • Polycystic Kidney Diseases / genetics*
  • Pregnancy
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*
  • Ultrasonography, Prenatal
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • Antigens, Neoplasm
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • Cep290 protein, human
  • Cytoskeletal Proteins
  • TCTN3 protein, human

Supplementary concepts

  • Meckel syndrome type 1