Chromosomal deletion syndrome
Chromosomal deletion syndromes result from
Examples of chromosomal deletion syndromes include
5p-Deletion
The chromosomal basis of Cri du chat syndrome consists of a deletion of the most terminal portion of the short arm of chromosome 5. 5p deletions, whether terminal or interstitial, occur at different breakpoints; the chromosomal basis generally consists of a deletion on the short arm of chromosome 5. The variability seen among individuals may be attributed to the differences in their genotypes. With an incidence of 1 in 15,000 to 1 in 50,000 live births, it is suggested to be one of the most common contiguous gene deletion disorders. 5p deletions are most common de novo occurrences, which are paternal in origin in 80–90% of cases, possibly arising from chromosome breakage during gamete formation in males[citation needed]
Some examples of the possible dysmorphic features include: downslanting palpebral fissures, broad nasal bridge,
4p-Deletion
The chromosomal basis of Wolf-Hirschhorn syndrome (WHS) consists of a deletion of the most terminal portion of the short arm of chromosome 4. The deleted segment of reported individuals represent about one half of the p arm, occurring distal to the bands 4p15.1-p15.2. The proximal boundary of the WHSCR was defined by a 1.9 megabase terminal deletion of 4p16.3. This allele includes the proposed candidate genes LEMT1 and WHSC1. This was identified by two individuals that exhibited all 4 components of the core WHS phenotype, which allowed scientists to trace the loci of the deleted genes. Many reports are particularly striking in the appearance of the craniofacial structure (prominent forehead, hypertelorism, the wide bridge of the nose continuing to the forehead) which has led to the descriptive term “Greek warrior helmet appearance.[citation needed]
There is wide evidence that the WHS core phenotype (growth delay, intellectual disability, seizures, and distinctive craniofacial features) is due to haploinsufficiency of several closely linked genes as opposed to a single gene. Related genes that impact variation include:
- WHSC1 spans a 90-kb genomic region, two-thirds of which maps in the telomeric end of the WHCR; WHSC1 may play a significant role in normal development. Its deletion likely contributes to the WHS phenotype. However, variation in severity and phenotype of WHS suggests possible roles for genes that lie proximally and distally to the WHSCR.
- WHSC2 (also known as NELF-A) is involved in multiple aspects of mRNA processing and the cell cycle
- SLBP, a gene encoding Stem Loop Binding Protein, resides telomeric to WHSC2, and plays a crucial role in regulating histone synthesis and availability during S phase.
- LETM1 has initially been proposed as a candidate gene for seizures; it functions in ion exchange with potential roles in cell signaling and energy production.
- FGFRL1, encoding a putative fibroblast growth factor decoy receptor, has been implicated in the craniofacial phenotype and potentially other skeletal features, and short stature of WHS.
- CPLX1 has lately been suggested as a potential candidate gene for epilepsy in WHS.[3]
Prader–Willi vs. Angelman Syndrome
Prader–Willi (PWS) and Angelman syndrome (AS) are distinct neurogenetic disorders caused by chromosomal deletions, uniparental disomy or loss of the imprinted gene expression in the 15q11-q13 region. Whether an individual exhibits PWS or AS depends on if there is a lack of the paternally expressed gene to contribute to the region.[citation needed]
PWS is frequently found to be the reason for secondary obesity due to early onset
AS is a severe debilitating neurodevelopmental disorder characterized by mental retardation, speech impairment, seizures, motor dysfunction, and a high prevalence of autism. The paternal origin of the genetic material that is affected in the syndrome is important because the particular region of chromosome 15 involved is subject to parent-of-origin imprinting, meaning that for a number of genes in this region, only one copy of the gene is expressed while the other is silenced through imprinting. For the genes affected in PWS, it is the maternal copy that is usually imprinted (and thus is silenced), while the mutated paternal copy is not functional.[5]
See also
References
- ^ "Chromosomal deletion syndromes". Archived from the original on 13 September 2013. Retrieved 16 September 2013.
- PMID 26235846.
- S2CID 29216104.
- PMID 26335514.
- PMID 22237428.