Although much progress has been made in research into the causes of behavioral and psychiatric disorders, the genetic causes remain relatively poorly understood. This is in part due to the genetic heterogeneity, variable phenotype, and complex inheritance of these disorders.
In order to get around this impasse, we are better characterizing families with inherited psychiatric conditions by studying and describing their physical, behavioural, and psychiatric presentation and by determining the underlying the genetic cause to their disease. By doing this, we hope to identify and better understand the biological pathways involved in behavioral and psychiatric disorders. Ultimately, this will help to identifying therapies for individuals suffering from these disorders.
Phenotypic, cytogenetic and molecular descriptions of unusual families
In collaboration with other clinicians, researchers, graduate students and volunteers, I am involved in trying to delineate the disease pathway of different families seen in the Medical Genetics clinic. As the interface with the affected families, I explain the transition from clinical care to research, recruit family members to participate, coordinate research testing, act as liaison with the laboratories, communicate with the families, and participate in the clinical and phenotypic description of the condition. The projects that I am currently involved in include:
The first characterization of the human phenotype associated with BRUNOL4 hemizygosity.
Characterization of a novel mutation in DCX in a female with lissencephaly whose features are more typical of an affected male.
Delineation of a novel mechanism in a three generation family with an apparently balanced reciprocal translocation (14;18) and mild intellectual disabilities and dysmorphic features. Further delineation of the breakpoints has identified the first known human mutation of the estrogen receptor 2 gene.
Phenotypic and genetic characterization of a child with profound pre- and postnatal growth retardation. This study has identified new disease loci at the breakpoints of a reciprocal translocation involving chromosomes 6 and 12.
Phenotypic, behavioral and molecular description of a family with a novel 19p13 duplication with large stature, severe learning difficulties, and behavioural abnormalities.
Associated features and outcome of individuals with macrocephaly
We are conducting a retrospective chart review of patients referred to Medical Genetics who were noted to have macrocephaly to determine the association of macrocephaly with overgrowth, cognitive and behavioural function and malformations. We anticipate that this information will help guide future diagnostic protocols.
Phenotypic, molecular and biochemical characterization of a novel X-linked mental retardation, congenital anomaly and behavioural disturbance syndrome
We are investigating a five-generation XLMR family where affected boys present with dysmorphic features and behavioral problems. Carrier females have normal cognition but demonstrate aggressive behaviour. We have isolated the causative mutation in the NSDHL gene, which is part of the cholesterol biosynthesis pathway. Along with other collaborators, we are presently trying to understand this pathway and its association with this family’s disease and aggressive behaviour in general.