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.
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.
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.
Base-pair positions can vary between genome assemblies. NCBI records place SETD5 and VHL within 3p25.3 on the current human reference assembly.
Genes in the Region
Genes in or around 3p25.3 include:
- 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
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.
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
References
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