Feldman, George J.
George J. Feldman, PhD, DMD
Curtis Building, Room 501
Philadelphia, PA 19107
Research and Clinical Interests
My lab is focused on identifying and understanding the causes of major crippling orthopaedic disorders that are genetically transmitted in families. Currently we are trying to find causative mutations for the complex disorder Developmental Dysplasia of the Hip (DDH). DDH is caused by the incomplete formation of the hip socket or acetabulum in individuals. This allows the head of the thigh bone or femur to easily dislocate and cause extra wear in the acetabulum often leading to osteoarthritis. While DDH is a complex disease to which environmental influences contribute, there is strong evidence of intergenerational transmission in human families. Although the overall prevalence of DDH in the US population is 1% in newborns undiagnosed DDH is thought to contribute to over 40% of all cases of osteoarthritis in young adults. Current screening tests in infants thus miss a large portion of affected individuals. Our goal is to develop genetic tests to detect the mutations that make an individual susceptible to this disorder. Early intervention with the Pavlik harness and other devices could then be used in these individuals to encourage acetabular development.
We are attempting to find causative mutations using 2 different approaches:
- Traditional linkage analysis. We have recruited a number of DDH affected families and have retrieved DNA from their peripheral blood and cheek swabs. We are using the Affymetrix platform to identify those single nucleotide polymorphisms that co-segregate with affected individuals but are absent from unaffected relatives.
- Some DDH affected individuals are more affected than others. We have identified a severely affected family some of whose members have bilateral DDH. We hypothesize that the severity of their disease might be explained by a variation in the copy number of larger segments of their DNA. To test this hypothesis we are planning to hybridize their DNAs to specifically designed Affymetrix chips to search for copy number variations that are shared by affected individuals but not by the unaffected relatives or other controls.
Most Recent Peer-Reviewed Publications
- A murine model for developmental dysplasia of the hip: Ablation of CX3CR1 affects acetabular morphology and gait
- Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in a large multi-generation family
- Developmental biology of the hip
- Developmental dysplasia of the hip: Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in all affected members of a large multigeneration family
- Variable Expression and Incomplete Penetrance of Developmental Dysplasia of the Hip. Clinical Challenge in a 71-Member Multigeneration Family.
- The otto aufranc award: Identification of a 4 Mb region on chromosome 17q21 linked to developmental dysplasia of the hip in one 18-member, multigeneration family
- Response to "mutations of the Noggin and of the activin A type I receptor genes in fibrodysplasia ossificans progressiva (FOP)" by Lucotte et al
- Over-expression of BMP4 and BMP5 in a child with axial skeletal malformations and heterotopic ossification: A new syndrome
- Erratum: A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva (Nature Genetics (2006) 38, (525-527))
- A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva
- The genetics of fibrodysplasia ossificans progressiva
- Exoneration of NF-κB dysregulation in fibrodysplasia ossificans progressiva
- Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva (FOP)
- Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31
- Erratum: Opiz G/BBB syndrome in Xp22: Mutations in the MID1 gene cluster in the carboxy-terminal domain (American Journal of Human Genetics (September 1998) 63 (703-710))
- Opitz G/BBB syndrome in Xp22: Mutations in the MID1 gene cluster in the carboxy-terminal domain
- Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22
- A novel phenotypic pattern in X-linked inheritance: Craniofrontonasal syndrome maps to Xp22
- Mutations in FGFR1 and FGFR2 cause familial and sporadic pfeiffer syndrome
- A gene for cleidocranial dysplasia maps to the short arm of chromosome 6