Jan 27 2010
Researchers at Signature Genomic Laboratories, which performs diagnostic
genetic testing of chromosome abnormalities in individuals with
unexplained physical and developmental disabilities, recently
characterized a broad spectrum of facial and brain anomalies in
individuals with chromosome aberrations associated with
holoprosencephaly.
“These results are exciting because they demonstrate how microarray
testing allows us to broaden the clinical spectrum associated with
various chromosome aberrations”
Holoprosencephaly is a disorder in which the forward-most portion of the
brain fails to fully divide into hemispheres (the right and left “sides”
of the brain) during embryonic development. Holoprosencephaly can vary
in severity: in its most severe form, in which the hemispheres
completely fail to divide, holoprosencephaly can adversely affect brain
function or result in death, whereas milder forms do not affect brain
function but can result in facial deformities.
Most studies of the genetic bases of holoprosencephaly have examined
groups of patients with clinical diagnoses of full holoprosencephaly.
Several candidate genetic regions have been identified in such these
studies, but such studies do not account for potential variability in
the severity of clinical features. Researchers at Signature Genomic
Laboratories took a novel “genotype-first” approach, identifying all
individuals with chromosome aberrations associated with
holoprosencephaly in their database of over 40,000 cases tested at their
laboratory and working with the referring physicians of each case to
determine the extent of holoprosencephaly, if present. The researchers
also searched their patient database for any cases referred for testing
because of holoprosencephaly.
The results of the study, which were published in the journal Human
Genetics, showed that most cases with holoprosencephaly had
deletions of one of four major holoprosencephaly genes, which is
consistent with previous studies. Interestingly, several individuals
with deletions of genes that had previously only been hypothesized to be
associated with holoprosencephaly had mild forms of the disorder, which
supports these genes’ association with holoprosencephaly. Conversely,
deletions of several candidate genes were present in individuals with no
form of holoprosencephaly, which suggests deletion of these genes alone
is not sufficient to cause the disorder. Researchers also identified a
previously unreported abnormality associated with holoprosencephaly, an
extra piece of DNA on one copy of chromosome 13, which was identified in
two individuals with holoprosencephaly, one with a full form of the
disorder and one with a mild form.
“These results are exciting because they demonstrate how microarray
testing allows us to broaden the clinical spectrum associated with
various chromosome aberrations,” said Lisa G. Shaffer, Ph.D., President
and CEO of Signature Genomic Laboratories and senior author of the
study. “In the past, individuals were selected for study because they
displayed the clinical features that were thought to be typical of a
specific genetic disorder. Microarray analysis has allowed researchers
to expand the boundaries of 'typical' for some of these disorders.”
SOURCE Signature Genomic Laboratories
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