Abstract | INTRODUCTION: The clinical phenotype of the chromosome 2q31 deletion syndrome consists of limb anomalies ranging from monodactylous ectrodactyly, brachydactyly and syndactyly to camptodactyly. Additional internal organ anomalies-for example, heart defects, ocular anomalies-may be present. Hemizygosity for HOXD13 and EVX2 genes was thought to cause the observed skeletal defects. Recently, based on the phenotype of patients with overlapping 2q31 interstitial deletions, a new SHFM5 locus was proposed, proximal to the HOXD cluster, between EVX2 and marker D2S294. DLX1 and DLX2 haploinsufficiency was suggested as the most plausible explanation for the observed SHFM-like limb anomalies in these cases. METHODS AND RESULTS: Five unique, interstitial 2q31 deletion patients were selected to further characterise the 2q31 region and to establish a genotype/phenotype correlation map. The size of the deletions was delineated with a chromosome 2 specific tiling path bacterial artificial chromosome (BAC) array. The clinical and molecular data for this group of patients were compared to others in the literature. A common locus for the observed skeletal anomalies, including the HOXD genes and surrounding regulatory sequences, was delineated. These results correlate with recently published studies in animal models. In addition, a critical region for the facial gestalt of the 2q31.1 microdeletion syndrome was delineated. CONCLUSIONS: These results reinforce the hypothesis that the variable skeletal phenotype in 2q31 deletion patients is a result of hemizygosity for the HOXD genes and that the 2q31.1 microdeletion syndrome is a well defined and clinically recognisable phenotype.
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Authors | Boyan Dimitrov, Irina Balikova, Thomy de Ravel, Hilde Van Esch, Maryse De Smedt, Emiel Baten, Joris Robert Vermeesch, Irena Bradinova, Emil Simeonov, Koen Devriendt, Jean-Pierre Fryns, Philippe Debeer |
Journal | Journal of medical genetics
(J Med Genet)
Vol. 48
Issue 2
Pg. 98-104
(Feb 2011)
ISSN: 1468-6244 [Electronic] England |
PMID | 21068127
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- EVX2 protein, human
- HOXD13 protein, human
- Homeodomain Proteins
- Transcription Factors
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Topics |
- Abnormalities, Multiple
(genetics, pathology)
- Chromosome Deletion
- Chromosome Disorders
(genetics, pathology)
- Chromosomes, Artificial, Bacterial
- Chromosomes, Human, Pair 2
(genetics)
- Comparative Genomic Hybridization
- Female
- Hemizygote
- Homeodomain Proteins
(genetics)
- Humans
- In Situ Hybridization, Fluorescence
- Infant, Newborn
- Limb Deformities, Congenital
(genetics, pathology)
- Male
- Phenotype
- Syndrome
- Transcription Factors
(genetics)
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