COG6-CDG: Novel variants and novel malformation
Lara Cirnigliaro1, Paolo Bianchi2, Luisa Sturiale3
1Child Neurology and Psychiatry Section, Department of Clinical and Experimental Medicine, University of Catania, Catania.
Birth Defects Research
|January 24, 2022
Summary
Conserved Oligomeric Golgi (COG) subunit deficiency causes protein glycosylation defects. This study identifies novel COG6 mutations in a patient with a rare recto-vaginal fistula, expanding the known COG6-CDG spectrum.
Area of Science:
- Genetics
- Biochemistry
- Developmental Biology
Background:
- Conserved Oligomeric Golgi (COG) subunit deficiencies (COG-CDG) cause N- and O-protein glycosylation defects.
- COG-CDG patients exhibit neurological, multisystemic, and malformation issues.
- COG6-CDG, caused by COG6 mutations, is rare, with only 18 cases previously reported.
Observation:
- A newborn female presented with facial dysmorphism, distal arthrogryposis, and a recto-vaginal fistula.
- Clinical features included developmental delay, corpus callosum dysgenesis, liver/gastrointestinal issues, hyperthermia, and early demise.
- Serum glycosylation analysis revealed significant Golgi disarrangement.
Findings:
- Two novel COG6 variants were identified: c.823delA (frameshift, premature stop) and c.1141_1143delCTC (in-frame deletion).
- The patient exhibited a congenital recto-vaginal fistula, a malformation not previously associated with COG6-CDG or other COG defects.
- These findings expand the genetic and phenotypic spectrum of COG6-CDG.
Implications:
- This report broadens the understanding of the genetic landscape of COG6-CDG.
- The identification of a recto-vaginal fistula expands the spectrum of malformations associated with COG defects.
- Further research into COG subunit functions is crucial for understanding glycosylation disorders.
Related Concept Videos
01:43Sex-linked Disorders
103.4K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
103.4K
02:26Comparing Copy Number Variations and SNPs
18.0K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
18.0K
01:43Incomplete Dominance
26.2K
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.
26.2K
01:30Point and Frameshift Mutations
229
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
229
02:59Animal Mitochondrial Genetics
8.2K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
8.2K
01:07Teratogenicity
3.0K
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
3.0K