Gail Bruns, MD/PhD
Associate Professor of Pediatrics
Harvard Medical School/Children's Hospital
Department of Pediatrics (Genetics)

MRRC Project(s)

R01 HD33547-12
Genes, Chromosomal Regions And Developmental Disorders

This laboratory has focused on three areas of research - 1) the WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) contiguous gene syndrome; 2) identification, by cross-phylum database search, of human genes that define previously unrecognized ancient conserved sequences; and 3) mutation analysis of the RPGR and RP2 genes in X-linked retinitis pigmentosa.

Contiguous gene syndromes are multisystem developmental disorders that are associated with deletions of specific chromosomal regions. One of the best characterized of these is the WAGR syndrome with deletions involving distal 11p12-distal 11p14. This region encodes genes important for normal development of the kidney, genitourinary system, eye and brain, as well as other loci with roles in growth and in skeletal development. Molecular analysis of 11p13, in this and other laboratories, led to isolation of the Wilms tumor and aniridia genes, which specify transcription factors with important roles in development of the renal system and the eye. More recent work directed toward the mental retardation component of the syndrome resulted in definition of a new class of neural loci with predominant expression in developing brain. Recognition of this new gene family, which has extensive homology in the C. elegans genome, led this laboratory to seek other human genes that encode previously unrecognized "class marking" ancestral protein sequences by cross-phylum database searches, the second area of research in this laboratory.

Inherited retinitis pigmentosa (RP) is a frequent genetic eye disorder with an incidence of -1/3500. The inheritance patterns are: autosomal recessive (82%); autosomal dominant (10%); and X-linked (8%). Two loci for X-linked RP map to the p11.3-11.4 region of the short arm of the X-chromosome: the RP2 locus and the RP3 locus. The RPGR gene, which encodes a protein with homology to the RCC1 guanine nucleotide exchange factor for the GTPase protein Ran, was identified by others as an RP3 gene, and the RP2 gene was found to specify a protein similar to cofactor C involved in b-tubulin folding.