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Rhizomelic Chondrodysplasia Punctata Type 1, Genetic Testing

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a rare genetic disorder under peroxisomal biogenesis disorders (PBDs). Skeletal abnormalities, intellectual disability, and distinctive facial features characterize this condition. Rhizomelic chondrodysplasia punctata type 1 is caused by mutations in the PEX7 gene, which plays a crucial role in peroxisome function. The prevalence of RCDP1 is estimated to be 1 in 100.000 individuals.

Rhizomelic chondrodysplasia punctata type 1 genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).

The key features and aspects of rhizomelic chondrodysplasia punctata type 1 are:

  • Skeletal Abnormalities: Individuals with rhizomelic chondrodysplasia punctata type 1 typically exhibit rhizomelic shortening of the limbs, which means that the proximal parts of the limbs (such as the upper arms and thighs) are shorter than the distal parts. Joint contractures and other skeletal anomalies may also be present.
  • Facial Features: The features associated with RCDP1 may include a prominent forehead, a flattened nose bridge, a small nose with upturned nostrils, and a small mouth.
  • Intellectual Disability: Intellectual disability is a common feature of RCDP1. The severity can vary, and affected individuals may have developmental delays.
  • Peroxisomal Dysfunction: Peroxisomes are cellular organelles involved in various metabolic processes, including breaking certain fatty acids. Mutations in the PEX7 gene lead to impaired peroxisome function, resulting in the accumulation of substances called phytanic acid and very long-chain fatty acids in the body.
  • Diagnosis: Diagnosis of RCDP1 is typically based on clinical features, radiological findings, and confirmation through genetic testing to identify mutations in the PEX7 gene.
  • Treatment: There is no cure for RCDP1, and treatment focuses on managing symptoms and providing supportive care. This may include addressing skeletal abnormalities, physical therapy, and interventions to support cognitive and developmental needs.
More Information

Peroxisomes are cellular organelles that contain enzymes involved in beta-oxidation. Patients with rhizomelic chondrodysplasia punctata type 1 have pathogenic variants in the PEX7 gene, which codes for peroxin 7, a protein involved in the transport of certain enzymes into the organelle (such as PTS2, PHYH, and ACAA1). RCDP is also characterized by a reduced capacity for synthesizing plasmalogens, which are membrane phospholipids involved in the structure and functions of the cell membrane.

Approximately 80 pathogenic variants in the PEX7 gene have been described. Of these, c.875T>A (p.Leu292Ter) is the most common RCDP1-causing variant in the United States and Europe. This variant generates an early stop codon that produces a truncated and, therefore, non-functional protein. Patients with two copies of this mutation have deficient levels of plasmalogen and RCDP1 with the classic phenotype.

On the other hand, the variants c.903+1G>C (IVS9DS) and c.653C>T (p.Ala218Val) account for 17% of the mutant alleles. The former produces a change in the mRNA cleavage and splicing site of the last intron, generating an altered protein product. The second generates a protein change at codon 218, which, in homozygosis or combined with other mutations in the PEX7 gene, is associated with RCDP. The present test studies both.

The variant c.649G>A (p.Gly217Arg) results in a non-conservative amino acid change, generating a defective protein unable to reach the peroxisome. Its allelic frequency is approximately 4% in affected individuals.

The c.345T>G(p.Tyr115Ter) mutation produces a premature stop codon, resulting in a truncated form of the protein, and has been identified in patients with rhizomelic chondrodysplasia punctata type 1.

Rhizomelic chondrodysplasia punctata type 1 genetic testing analyzes the five most frequent pathogenic mutations of the PEX7 gene.

The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).

Additional information
Results Time4 - 5 Weeks
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