4 UW Hindbrain Malformation Research Program

Welcome to the University of Washington Hindbrain Malformation Research Program website.

We study the biology of hindbrain malformations and neurodevelopmental disorders such as Joubert syndrome, rhombencephalosynapsis, pontine tegmental cap dysplasia, and Chudley-McCullough syndrome to advance our understanding of brain development and improve the lives of families affected by these conditions. Identifying the causes of these disorders will provide better diagnostic and prognostic information to families and, we hope, lead to better treatments in the future. Please contact us for more information or to participate in our research.

Assist our research with your prenatal pregnancy imaging

As part of our ongoing research studies, we are trying to improve prenatal diagnosis of Joubert syndrome. We intend to compare imaging studies (ultrasound and fetal MRI) from pregnancies affected by Joubert syndrome and pregnancies unaffected by Joubert syndrome to identify the most accurate imaging features for diagnosis. If you have had prenatal imaging of affected or unaffected pregnancies and would like to participate, please contact usat (206) 616-3788 or joubert@uw.edu. Thank you!

Current percent of solved cases: 65%

Joubert syndrome is a “ciliopathy” because all of the Joubert syndrome genes seem to be involved with an important cellular structure called the primary cilium. The primary cilium acts as an antenna for most cells in the body, allowing the cells to detect the environment outside the cell and react to it. This diagram of a primary cilia represents the percent of “solved” Joubert syndrome cases, those where we have identified the mutations in the gene responsible for causing the disorder in that particular patient.

The Hindbrain Malformation Research Program recently published a comprehensive clinical and genetic description of >500 patients with Joubert syndrome (JS) enrolled over the past 20 years:

Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.

The paper presents detailed clinical information from this cohort, and we determined that 66% of people with JS have at least one non-neurological issue (usually retinal dystrophy, kidney disease, liver fibrosis, polydactyly, and encephalocele), leaving 34% of individuals with .pure. JS. We sequenced 27 Joubert-associated genes in >400 individuals from 375 families, identifying 253 different causal mutations in 22 of the JS genes, and identifying the first mutations in the B9D2 gene. While some genetic causes were associated with specific clinical features, it is not possible to determine with certainty which gene is affected based on clinical findings. The genetic cause is helpful for guiding the frequency of monitoring for medical complications. This paper describes by far the largest cohort of patients to date and provides valuable information for patients, families, and clinicians to enable diagnostic, carrier and prenatal testing, guide medical monitoring for complications, and develop gene-specific treatments of the future through understanding the underlying biological mechanisms.

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© 2017 Hindbrain Malformation Research Program, Department of Pediatrics, University of Washington
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