Exome sequencing and RNA analysis identify two novel CPLANE1 variants causing Joubert syndrome
Hongjun Fei1, Yi Wu1, Yanlin Wang1
1Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Molecular Genetics & Genomic Medicine
|January 29, 2022
Summary
Joubert syndrome (JS) research identified two new CPLANE1 gene variants. One variant causes abnormal RNA splicing, deepening understanding of JS molecular mechanisms.
Area of Science:
- Genetics
- Molecular Biology
- Medical Genetics
Background:
- Joubert syndrome (JS) is a complex genetic disorder with over 35 known causative genes.
- Limited research exists on the pathogenic mechanisms of JS-associated genetic variants.
- RNA splicing analysis is crucial for understanding the functional impact of noncanonical splicing variants.
Purpose of the Study:
- To investigate the genetic etiology and pathogenic mechanisms of Joubert syndrome in a patient family.
- To identify and functionally characterize novel variants in the CPLANE1 gene associated with JS.
Main Methods:
- Whole exome sequencing (WES) was employed to screen for causative gene variants.
- Sanger sequencing was used for variant verification.
- Functional experiments, including RNA splicing analysis, were conducted to assess variant pathogenicity.
Main Results:
- Two novel heterozygous CPLANE1 variants, c.4459del (frameshift) and c.7534-14G>A (intronic), were identified in the JS patient.
- The c.4459del variant was classified as likely pathogenic.
- The intronic variant c.7534-14G>A was found to cause aberrant exon 37 skipping, leading to a truncated protein.
Conclusions:
- The study expands the known spectrum of CPLANE1 variants in Joubert syndrome.
- The findings enhance the understanding of JS molecular pathogenesis, particularly the role of RNA splicing.
- Diagnostic WES is confirmed as a significant tool for identifying JS-related genetic variations.
More Related Videos
Related Concept Videos
01:33Pleiotropy
41.4K
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,...
41.4K
01:23Cystic Fibrosis: Pathogenesis
387
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
387
01:05Single Nucleotide Polymorphisms-SNPs
16.6K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
16.6K
02:53CRISPR and crRNAs
17.6K
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
17.6K
02:24Ribosome Profiling
3.7K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.7K
02:15Experimental RNAi
6.3K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.3K