Refinement of the Region for Split Hand/Foot Malformation 5 on 2q31.1
A Theisen1, J A Rosenfeld, K Shane
1Signature Genomic Laboratories, Spokane, Wash.
Molecular Syndromology
|December 6, 2011
Summary
Microdeletions at 2q31.1 are linked to developmental delays and neurological deficits. Hand and foot anomalies in these patients are primarily caused by HOXD cluster deletions, not DLX1/DLX2.
Area of Science:
- Genetics
- Developmental Biology
- Clinical Medicine
Background:
- 2q31.1 microdeletions are associated with a syndrome featuring intellectual disability, microcephaly, cleft palate, growth delay, and limb anomalies.
- Genes in the 2q31.1 region, including HOXD and DLX1/DLX2, have been implicated in split hand-foot malformation 5 (SHFM5).
Purpose of the Study:
- To clarify the genotype-phenotype correlations of deletions within the 2q31.1 region.
- To determine the specific genes responsible for hand/foot anomalies in 2q31.1 microdeletion syndrome.
Main Methods:
- Identified 14 individuals with 2q31.1 deletions using microarray analysis.
- Correlated deletion locations with clinical phenotypes, focusing on neurological and skeletal features.
- Compared phenotypes between deletions encompassing the HOXD cluster versus those including DLX1/DLX2.
Main Results:
- All subjects exhibited neurological deficits.
- Seven subjects with HOXD cluster deletions showed varying degrees of hand/foot anomalies (syndactyly, brachydactyly, ectrodactyly).
- Five subjects with deletions proximal to HOXD, including DLX1/DLX2, had no significant hand/foot anomalies.
- Dysmorphic facial features were not consistently observed, contrary to previous reports.
Conclusions:
- Haploinsufficiency of the HOXD cluster is the likely cause of skeletal abnormalities in 2q31.1 microdeletion syndrome.
- Deletions involving DLX1/DLX2 alone do not appear to cause the characteristic hand/foot malformations.
