Genetic basis unknown in many children with mental retardation and developmental delays

Researchers from four laboratories that perform diagnostic genetic testing of chromosome abnormalities in individuals with unexplained physical and developmental disabilities recently identified a previously unrecognized genetic disorder.

“In a substantial proportion of children with mental retardation and developmental delays, the genetic basis is unknown”

In their study, published in the American Journal of Human Genetics, researchers at Signature Genomic Laboratories, Nationwide Children’s Hospital, Emory University School of Medicine and Baylor College of Medicine independently identified a total of seven individuals with nearly identical-sized deletions, or missing sections of DNA, on one of their two copies of chromosome 17. None of the children’s parents had the section of DNA missing, which suggests the anomaly is causative of the children’s physical and developmental disabilities which included a combination of developmental delays including speech delay, postnatal growth retardation, heart defects and hand, foot and limb abnormalities.

The researchers estimate the incidence of this genetic abnormality in the general population to be approximately 1 in 115,000.

Two of the genes in the deleted region were of particular interest to researchers because of their potential role in the heart and limb anomalies in the children. TBX2 and TBX4 are members of a closely related gene family, the T-box genes, that is involved in development. Mutations of TBX4 have been identified in individuals with small patella syndrome, characteristic features of which include delayed tissue formation of the pelvic bones and femur and foot anomalies. Several other genetic disorders for which heart and limb defects are characteristic features have been associated with disruption of T-box genes, which led the researchers to suggest the newly reported disorder is a similar “heart-hand” syndrome.

“In a substantial proportion of children with mental retardation and developmental delays, the genetic basis is unknown,” said Dr. Blake C. Ballif, Director of Product Development and Research at Signature Genomic Laboratories and lead author of the study. “Therefore, the identification of a previously unknown genetic aberration sheds further light on the genetic basis of human disease, in addition to providing an answer for these children and their families.”

Said Dr. Ballif, “In addition, this report represents a collaborative academic effort by several otherwise competing diagnostic laboratories to disseminate important clinical and molecular information that significantly contributes to our understanding of the molecular basis of human genetic disease.”