1p36 deletion syndrome: an update
Valerie K Jordan1, Hitisha P Zaveri2, Daryl A Scott3
1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
Insights
1p36 deletion syndrome, a common condition in newborns, causes varied medical issues. Recent research identifies specific genes on chromosome 1p36 linked to these diverse phenotypes, aiding in understanding the syndrome.
Area of Science:
- Genetics
- Human Molecular Genetics
- Developmental Biology
Background:
- 1p36 deletion syndrome is the most common terminal deletion disorder, affecting 1 in 5,000 newborns.
- It presents with significant phenotypic variability, including developmental delay, intellectual disability, seizures, and congenital anomalies.
- This variability is partly due to genetic heterogeneity within the 1p36 region.
Purpose of the Study:
- To review recent advances in mapping genes and genomic regions responsible for 1p36 deletion phenotypes.
- To identify specific genes implicated in the diverse clinical manifestations of 1p36 deletion syndrome.
Main Methods:
- Review of recent scientific literature on 1p36 deletion syndrome.
- Analysis of array-based copy number variant data to identify deleted regions.
- Correlation of specific gene deletions with observed phenotypes.
Main Results:
- Array-based copy number variant analysis effectively identifies deleted regions on chromosome 1p36.
- Several genes, including MMP23B, GABRD, SKI, PRDM16, KCNAB2, RERE, UBE4B, CASZ1, PDPN, SPEN, ECE1, HSPG2, and LUZP1, are implicated in specific 1p36 deletion phenotypes.
- Phenotypic prediction based solely on deletion extent remains challenging due to unidentified genes and potential multi-gene effects.
Conclusions:
- Identifying genes within the 1p36 region is crucial for understanding the phenotypic variability of 1p36 deletion syndrome.
- Further research is needed to fully elucidate the genotype-phenotype correlations and identify all contributing genes.
- Advances in genetic analysis are improving our understanding of this complex chromosomal disorder.
Abstract:
Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are the most common terminal deletions in humans. Medical problems commonly caused by terminal deletions of 1p36 include developmental delay, intellectual disability, seizures, vision problems, hearing loss, short stature, distinctive facial features, brain anomalies, orofacial clefting, congenital heart defects, cardiomyopathy, and renal anomalies. Although 1p36 deletion syndrome is considered clinically recognizable, there is significant phenotypic variation among affected individuals. This variation is due, at least in part, to the genetic heterogeneity seen in 1p36 deletions which include terminal and interstitial deletions of varying lengths located throughout the 30 Mb of DNA that comprise chromosome 1p36. Array-based copy number variant analysis can easily identify genomic regions of 1p36 that are deleted in an affected individual. However, predicting the phenotype of an individual based solely on the location and extent of their 1p36 deletion remains a challenge since most of the genes that contribute to 1p36-related phenotypes have yet to be identified. In addition, haploinsufficiency of more than one gene may contribute to some phenotypes. In this article, we review recent successes in the effort to map and identify the genes and genomic regions that contribute to specific 1p36-related phenotypes. In particular, we highlight evidence implicating MMP23B, GABRD, SKI, PRDM16, KCNAB2, RERE, UBE4B, CASZ1, PDPN, SPEN, ECE1, HSPG2, and LUZP1 in various 1p36 deletion phenotypes.
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