Projects

Prader-Willi syndrome (PWS) is caused by a loss of genes normally expressed only from the paternal chromosome 15. About 70% of PWS cases arise from Type 1 and Type 2 deletions, which are about 5 million DNA base pairs in size. Genetic mapping data from unique patients harboring smaller deletions, “microdeletions”, in the PWS region implicate the...

Temper outbursts are commonly shown by people with Prader-Willi syndrome (PWS) and can cause great problems for people with the syndrome, their family members and caregivers. One common reason for temper outbursts is that people with PWS find changes to routines or to plans very difficult. This difficulty with change is linked to impairment in a...

Prader-Willi Syndrome (PWS) is a complex genetic disorder characterized by an insatiable feeling of hunger and an irrepressible urge to overeat. If left uncontrolled, hunger and overeating can lead to morbid obesity, diabetes, cardiovascular disease and premature death. Why PWS causes hunger is an important question that must be answered in we...

Prader-Willi syndrome (PWS) is a rare genomic imprinting disorder caused by an abnormality in the PWS critical region (PWSCR), a particular region of 15th chromosome (15q11-q13). Genomic imprinting refers to a phenomenon in which genes from specific parent can be expressed. PWSCR contains several imprinted genes that are only expressed from either...

Prader-Willi syndrome (PWS) is a genetic disease characterized by an insatiable appetite and a variety or behavioral dysregulations. It is known that the brain, and particularly a region of the brain called the hypothalamus, is important to regulating appetite and body weight. We also know that many key physiological processes, including appetite...

A remarkable clinical resemblance between Prader-Willi syndrome (PWS) and hypotonia-cystinuria syndrome (HCS) was observed in our multidisciplinary clinic for PWS in our center. All HCS patients were initially referred for genetic analysis of PWS. Patients with either syndrome suffer from weakness and poor sucking in the newborn period. This...

MAGEL2 is one of five genes in the Prader-Willi syndrome (PWS) critical domain on chromosome 15 that encodes a protein. Our group recently described a group of patients with mutations of MAGEL2 causing Prader-Willi features and autism. Autism spectrum disorder is seen in up to one third of individuals with PWS, and in all individuals with MAGEL2...

In Prader-Willi syndrome (PWS) the progression from poor appetite and failure-to-thrive (FTT) to obesity and voracious appetite is complex and takes several years. We have recently shown that there are 6 distinct post-natal nutritional phases in PWS. By looking at the end products of cellular processes in individuals with PWS before and after the...

Hyperphagia (extreme overeating) is the most significant factor contributing to obesity in Prader-Willi syndrome (PWS) and considered a cardinal feature. PWS is recognized as the most common syndromic cause of life-threating obesity, but no medications are currently available to decrease appetite or lessen obesity in PWS. Preliminary studies have...

Prader-willi syndrome is a genetic disorder caused by loss of a portion of a copy of chromosome 15. Common features include early problems with muscle weakness and feeding followed by occult weight gain without an increase in food consumption beginning during late infancy/early toddler period prior to the onset of hyperphagia. Recent research has...

The MAGEL2 gene appears as one of the main genes involved in feeding and behavioral (autistic like behavior) alterations observed in Prader-Willi Syndrome. We showed that, in mouse, the deficiency of Magel2 results in a phenotype similar to the clinical description of patients with mutations in MAGEL2. Indeed, we showed that Magel2-deficient mice...

The identification of genetic loci conferring susceptibility to Prader-Willi Syndrome (PWS) provides valuable opportunities for understanding its biological basis. A powerful approach for probing the roles of genes within the nervous system is to introduce them into mice. The resulting mouse models may be studied in depth to determine how genes...

The genetic disorder Prader-Willi syndrome (PWS), results in debilitating physical, endocrine, cognitive, and behavioral symptoms. Many of the characteristics of PWS, such as uncontrollable food intake, stunted growth, and emotional problems suggest that disruptions in brain regions such as the hypothalamus may cause this. Recently, the gene...

This proposal will investigate the development of a gene therapy for Prader-Willi syndrome (PWS). PWS is caused by the loss of a region of human chromosome 15q11-13. Humans have two copies of chromosome 15, one the mother (maternal) and one from the father (paternal). Due to an unusual mechanism called genetic imprinting, the genes affecting PWS...

Prader-Willi Syndrome (PWS) is a rare disorder, sharing common genes with autism and schizophrenia; patients with PWS are at a high risk of developing psychiatric illnesses and behavioral problems, however, the underlying neurobiology that places them at-risk is yet unknown. Here we propose a cross-sectional, multi-faceted brain imaging study in...

Once Prader-Willi patients reach the stage where hyperphagia is a dominant characteristic of the disease, the progression to obesity, morbid obesity and diabetes and their complications reduces the quality of life of the patient and increases their risk of death from a number of causes. The constant food seeking and food obsession combined with...