| |
 |
Summary of NPHP1 Gene Identification
Our group in Seattle, working in conjunction with Drs.
Bill Dobyns and Joseph Gleeson, has identified the first
gene change associated with Joubert syndrome. This has
been published in the July issue of the American Journal
of Human Genetics (Parisi et al., “The NPHP1 gene
deletion associated with juvenile nephronophthisis is
present in a subset of individuals of with Joubert
syndrome,” Am. J. Hum. Genet., 2004, 75:82-91). The
gene, called NPHP1, has been known to cause a kidney
disease known as juvenile nephronophthisis.
Approximately 60-80% of children with nephronophthisis
are missing both copies of the NPHP1 gene. Because some
children with Joubert syndrome develop nephronophthisis,
we tested children with kidney involvement for deletions
in this gene. We found this change in 1 out of 25
children who were tested, and this child had
nephrophthisis and a mild form of Joubert syndrome. When
we tested 80 children with Joubert syndrome whether or
not they kidney involvement, we found a total of 2
children with this deletion. This result has been
confirmed by Dr. Valente’s group in Italy in a child
with Joubert syndrome, retinal dystrophy, and
nephronophthisis.
Nephronophthisis is a form of kidney disease that is
also known as medullary cystic kidney disease. It can be
progressive. The symptoms may not be apparent until late
childhood or early teenage years. The first symptoms are
usually difficulty with concentrating the urine and
sometimes anemia (low red blood cell count). This is why
we recommend a complete blood count (to check hematocrit
for evidence of anemia) as well as blood tests to check
for kidney function (creatinine and BUN) and ultrasound
examination. We also recommend a urine test to check its
concentration in a sample collected when a child first
wakes up (when it should be most concentrated). Later in
the disease, there may be ultrasound changes such as
scarring of the kidneys. Sometimes, very small cysts can
be visualized in the middle of the kidney that may
suggest this condition. Treatments can include
medications, dialysis, and sometimes, a kidney
transplant. Nephrologists or kidney doctors are the best
doctors to manage this condition.
Therefore, we believe that the NPHP1 deletion represents
the first molecular defect identified in a subset of
children with Joubert syndrome. Children with
nephronophthisis and retinal disease are at greater risk
to have this genetic cause. It may also be more likely
in children with milder neurologic symptoms of Joubert
syndrome. However, it is important to remember that this
is a very uncommon cause of Joubert syndrome, as
probably less than 5% of children will have this gene
deletion. We are developing recommendations for
screening children with Joubert syndrome for this gene
deletion. Genetic testing is probably warranted,
particularly for those families interested in prenatal
diagnosis, since the presence of an NPHP1 gene deletion
in an older affected child would allow prenatal DNA
testing as an option for first trimester diagnosis in
subsequent pregnancies. We recommend annual blood and
urine screening tests and ultrasound exam as outlined
above for all children with Joubert syndrome. Please
contact us or refer to the “Recommendations for
evaluation and monitoring of patients with Joubert
syndrome and related disorders” provided on the Joubert
Syndrome Foundation website for further details.
Submitted by Melissa Parisi, MD, PhD and Ian Glass, MD,
University of Washington, Seattle, WA
Back to Physician
Research Page |
|
|
Printer friendly
version |
| |
|
The views expressed do
not necessarily reflect those of the donors. The articles,
announcements, and resources included on this website are
for information only and should not be considered as medical
advice. Please always consult your physician for medical
advice. The Joubert Syndrome Foundation & Related Cerebellar
Disorders does not endorse any product, service, or theory
referred to on the website.
|