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2q31.1 microdeletion syndrome

Journal Contribution - Journal Article

Subtitle:redefining the associated clinical phenotype

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.

Journal: J Med Genet
ISSN: 0022-2593
Issue: 2
Volume: 48
Pages: 98-104
Keywords:Abnormalities, Multiple/genetics, Chromosome Deletion, Chromosome Disorders/genetics, 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, Male, Phenotype, Syndrome, Transcription Factors/genetics