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.”
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