Theme: iWiki Log in Register

Diff: Chromosome 3p25.3

Comparing revision #1 (2023-06-09 23:55:30) with revision #2 (2026-06-22 10:20:41).

Old	New
	'''Chromosome 3p25.3''' is a cytogenetic band on the short arm of human chromosome 3. The notation means chromosome 3, short arm '''p''', region 2, band 5, sub-band 3.

Chromosome 3p25.3 is a specific region on the short arm (p) of human chromosome 3. It spans from base pair position 8,750,000 to 10,250,000 on chromosome 3, according to the GRCh38/hg38 human reference genome assembly. This region contains several genes and has been implicated in various genetic disorders and diseases.
	The region is clinically important because it includes genes such as SETD5 and VHL. Deletions involving this part of chromosome 3 can contribute to developmental and medical features seen in 3p deletion syndromes.

== Genes in Chromosome 3p25.3 ==
Several genes are located within the 3p25.3 region, and their functions contribute to various biological processes. Some of the notable genes in this region include:
	== Location and Notation ==
	Cytogenetic bands are chromosome addresses. They describe where a finding sits on a stained chromosome, but they are not the same thing as a single gene.

# [[CHRDL1]]: CHRDL1 (Chordin-Like 1) encodes a secreted protein involved in embryonic development and modulating the bone morphogenetic protein (BMP) signaling pathway. Mutations or dysregulation of CHRDL1 have been associated with X-linked megalocornea and implicated in certain cancers.
# [[MEGF10]]: MEGF10 (Multiple Epidermal Growth Factor-Like Domains 10) is involved in muscle development and is associated with a form of early-onset myopathy called early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). Mutations in MEGF10 disrupt normal muscle function and lead to muscle weakness and respiratory difficulties.
# [[C3orf67]]: C3orf67 (Chromosome 3 Open Reading Frame 67) is a gene with unknown function. Further research is needed to understand its role in cellular processes and human health.
# [[CEP70]]: CEP70 (Centrosomal Protein 70) is involved in centrosome biology and plays a role in proper cell division. It helps ensure the accurate distribution of genetic material during cell division, and its dysfunction can lead to abnormalities in cell division and genomic instability.
	Base-pair positions can vary between genome assemblies. NCBI records place SETD5 and VHL within 3p25.3 on the current human reference assembly.

== Clinical Significance ==
Alterations in chromosome 3p25.3 have been associated with various genetic disorders and diseases. Chromosomal rearrangements, such as deletions or duplications, involving this region can lead to genetic conditions with diverse clinical presentations. Some examples include:
	== Genes in the Region ==
	Genes in or around 3p25.3 include:

# [[3p- Syndrome]]: The deletion of a portion of chromosome 3p25.3 can result in a syndrome known as 3p- syndrome or 3p deletion syndrome. This condition is characterized by developmental delay, intellectual disability, distinctive facial features, growth retardation, and other physical abnormalities.
# [[EMARDD]]: Mutations in the MEGF10 gene within the 3p25.3 region have been associated with early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). This rare condition manifests with muscle weakness, respiratory difficulties, feeding problems, and delayed motor milestones.
# Other Disorders: Chromosomal rearrangements involving 3p25.3 have been implicated in other conditions, such as intellectual disability, autism spectrum disorders, and various types of cancer. The specific genes and mechanisms underlying these associations require further investigation.
	* '''SETD5''', a gene associated with intellectual developmental disorder and with the core phenotype of 3p25.3 microdeletion syndrome when one copy is lost
	* '''VHL''', a tumour suppressor gene associated with von Hippel-Lindau syndrome when pathogenic variants are present

== Research and Future Perspectives ==
Ongoing research continues to shed light on the functions of genes within the 3p25.3 region and their implications in human health and disease. Advances in molecular genetics and genome sequencing technologies are enabling researchers to better understand the genetic basis of conditions associated with chromosome 3p25.3 alterations.
	Imported text previously listed [[MEGF10]] and [[CHRDL1]] as genes in this region. That was incorrect. MEGF10 is on chromosome 5q23.2, and CHRDL1 is on Xq23.

Further studies are needed to elucidate the precise roles of genes in this region and their interactions with other genes and environmental factors. The insights gained from such research may contribute to the development of diagnostic tools, therapeutic approaches, and genetic counseling for individuals affected by conditions associated with chromosome 3p25.3.
	== 3p25.3 Microdeletion ==
	Microdeletions involving 3p25.3 can cause a rare chromosomal disorder. Reported features include intellectual disability, delayed development, poor speech, seizures or abnormal EEG findings, ataxia and stereotyped hand movements.

	Larger 3p deletions can involve additional bands and genes, so the clinical picture can be broader. The exact deletion size and gene content are important for interpretation.

	== SETD5 ==
	SETD5 is one of the key genes discussed in relation to 3p25.3. NCBI places SETD5 at 3p25.3 and describes pathogenic loss-of-function variants as associated with an autosomal dominant form of intellectual disability.

	Unique and other rare-chromosome resources describe SETD5 as one of the genes missing in some 3p25 deletions. Loss of one working copy is thought to explain many of the developmental features seen in 3p25.3 microdeletion syndrome.

	== VHL ==
	VHL is also located at 3p25.3. The gene encodes a tumour suppressor protein involved in oxygen-response pathways, including regulation of hypoxia-inducible factors.

	Pathogenic variants in VHL can cause von Hippel-Lindau syndrome, a hereditary tumour-predisposition condition involving haemangioblastomas, renal cysts and renal cell carcinoma, phaeochromocytoma, pancreatic neuroendocrine tumours and other features.

	== Testing and Interpretation ==
	Findings in 3p25.3 may be detected by chromosomal microarray, sequencing, deletion and duplication testing, or wider genomic testing. Interpretation depends on whether the result is a single-gene variant, a deletion, a duplication or a larger chromosomal rearrangement.

	Genetic counselling is often important because recurrence risk depends on whether the change arose de novo or was inherited from a parent with a balanced rearrangement or variant.

	== See Also ==
	* [[3p-_Syndrome]]
	* [[Chromosome_3]]
	* [[Genetic_Disorder]]

== References ==	== References ==
	* [https://www.ncbi.nlm.nih.gov/gene/55209 NCBI Gene: SETD5]
	* [https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Db=gene&Term=7428 NCBI Gene: VHL]
	* [https://medlineplus.gov/genetics/condition/3p-deletion-syndrome/ MedlinePlus Genetics: 3p deletion syndrome]
	* [https://rarechromo.org/media/information/Chromosome%20%203/3p25deletions%202022%20FTNW.pdf Unique: 3p25 deletions]
	* [https://www.orpha.net/en/disease/detail/435638 Orphanet: Proximal 3p25.3 microdeletion syndrome]
	* [https://www.ncbi.nlm.nih.gov/books/NBK1463/ GeneReviews: Von Hippel-Lindau Syndrome]

# Ou Z, Stankiewicz P, Xia Z, et al. Observation and prediction of recurrent human translocations mediated by NAHR between nonhomologous chromosomes. Genome Res. 2011;21(1):33-46. doi:10.1101/gr.109157.110.
# El-Hattab AW, Schaaf CP, Fang P, et al. Clinical characterization of int22h1/int22h2-mediated Xq28 duplication/deletion: new cases and literature review. BMC Med Genet. 2011;12:160. doi:10.1186/1471-2350-12-160.
# Zhang C, Cai Y, Qi J, et al. A case of 3p25.3 microdeletion with novel features: Insights into the clinical phenotype and genetic basis. Mol Genet Genomic Med. 2020;8(2):e1097. doi:10.1002/mgg3.1097.
	[[Category:Genetics]]
	[[Category:Chromosomes]]
	[[Category:Medicine]]