Prader-Willi syndrome, deletion subtypes, and magnesium: Potential impact on clinical findings
Merlin G Butler1, Neil Cowen2, Anish Bhatnagar2
1Department of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, Kansas, USA.
Insights
Prader-Willi syndrome (PWS) patients with Type I deletion show lower magnesium levels than Type II. This may explain neurobehavioral differences and metabolic issues in PWS subtypes.
Area of Science:
- Genetics
- Neuroscience
- Endocrinology
Background:
- Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic imprinting disorder.
- PWS is characterized by hypotonia, failure to thrive, learning/behavioral issues, and hyperphagia leading to obesity.
- Two distinct deletion types (Type I and Type II) in the 15q11-q13 region are associated with varying clinical severity.
Purpose of the Study:
- To investigate plasma magnesium levels in PWS participants with Type I versus Type II 15q11-q13 deletions.
- To explore the potential link between magnesium levels, gene deletions, and clinical manifestations in PWS.
- To assess the impact of magnesium transporter gene absence on PWS subtypes.
Main Methods:
- Measured baseline plasma magnesium levels in a cohort of PWS participants.
- Analyzed data stratified by the presence of Type I or Type II 15q11-q13 deletions.
- Compared magnesium levels between PWS subgroups and correlated findings with clinical severity.
Main Results:
- PWS participants with the larger Type I deletion exhibited significantly lower plasma magnesium levels compared to those with the Type II deletion.
- Females with Type I deletion showed more pronounced lower magnesium levels than females with Type II deletion.
- Despite differences, magnesium levels remained within the normal range for both PWS subgroups.
Conclusions:
- Lower plasma magnesium in PWS Type I deletion may contribute to more severe neurobehavioral problems.
- The absence of magnesium transporter genes in Type I deletion could impact magnesium homeostasis.
- These magnesium level differences may influence glucose and insulin metabolism, contributing to PWS comorbidities.
Abstract:
Prader-Willi syndrome is a complex neurodevelopmental genetic imprinting disorder with severe congenital hypotonia, failure to thrive with learning and behavioral problems, and hyperphagia with obesity developing in early childhood. Those with the typical 15q11-q13 Type I deletion compared with the smaller Type II deletion have more severe neurobehavioral problems and differ by the absence of four genes in the 15q11.2 BP1-BP2 region. Two of the genes encode magnesium transporters supporting brain and neurological function and we report on magnesium levels in the two deletion groups of PWS participants. We measured baseline plasma magnesium and analyzed data from a PWS cohort with and without the Type I or Type II deletion. Significantly lower plasma magnesium levels were found in PWS participants with the larger Type I deletion and more so with females with Type I deletion compared with females having the Type II deletion, although magnesium levels remained within normal range in both subgroups. Those with PWS and the larger 15q11-q13 Type I deletion were more clinically affected than those with the smaller Type II deletion. Two of the four genes missing in those with the larger deletion code for magnesium transporters and may impact magnesium levels. Our study showed lower magnesium levels in those with the larger deletion which could contribute to neurobehavioral differences seen in the two separate 15q11-q13 deletion subtypes and in addition affect both glucose and insulin metabolism impacting comorbidities but will require more research.
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