Genetic Testing and Phenotypic Characterization of Severely Obese Pediatric and Adult Volunteers

Study Overview
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Brief Summary
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The purpose of this screening study is to identify people who have a rare genetic cause of obesity - specifically three genetic variants (a change in the DNA structure) of the POMC, PCSK1 and LepR genes that are currently known to result in obesity. This screening study will not include any investigational drugs. You will be asked to provide a DNA sample and answer some questions about your medical history and hunger.

Official Title
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Genetic Testing and Phenotypic Characterization of Severely Obese Pediatric and Adult Volunteers

Conditions
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Pro-opiomelanocortin (POMC), Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1) and Leptin Receptor (LepR) Gene Mutations

Participation Criteria
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Eligibility Criteria
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Individuals who meet any of the following inclusion criteria may be eligible: Participant aged 2 or older. Study participant and/or parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and be able to understand and sign the written informed consent/assent. ≥40kg/m2 (age 18 and older) or 1.4x 95th percentile of BMI for age (ages 2-17) - with evidence of hunger or hyperphagia by screening surveys, indicated by a patient or observer score at or greater than midpoint of scale. o Individuals with clinical evidence of RGDO (per appendix 4) but do not meet the BMI criteria may be included if the investigators estimation and proband demonstrates a BMI Z-score difference of >1 between proband and any other sibling; and/or the proband demonstrates a BMI difference >10 kg/m2 between proband and parents. ≥50 kg/m2 (age 18 and older) or 1.5x 95th percentile of BMI for age (ages 2-17). Cohorts included under this criteria include ≥50-60 kg/m2 (age 18 and older) or 1.5x 95th percentile of BMI for age (ages 2-17) and ≥60 kg/m2 (age 18 and older) or 1.6x 95th percentile of BMI for age (ages 2-17). ≥ 40 kg/m2 (pre-operative) or 1.4x 95th percentile of BMI for age (ages 12-17) with history of bariatric surgery or planned surgery within 3 months (prior to or following screening). Individuals who meet any of the following exclusion criteria will not be eligible: Prior craniopharyngioma or other hypothalamic brain region surgery or surgeries/procedures for brain tumor, i.e., ventriculoperitoneal shunt and radiation therapy Diagnosis of Prader-Willi syndrome

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>If the subject has a history of hyperphagia, early onset obesity and/or clinical characteristics known to be related to mutations in the MC4R pathway and related to obesity (1.4 times 95th percentile in children). | |
| Cohort 2<br>If the subject has exponentially high BMI (≥50 to 59), without hyperphagia and early onset obesity, whose obesity may be driven by an MC4R pathway mutation in the absence of other clear history or clinical characteristics (1.5 - 1.6 times 95th percentile in children). | |
| Cohort 3<br>If the subject has exponentially high BMI (≥60), without hyperphagia and early onset obesity, whose obesity may be driven by an MC4R pathway mutation in the absence of other clear history or clinical characteristics (1.6 times 95th percentile in children). | |
| Cohort 4<br>If the subject has had or is undergoing bariatric surgery, who represents a refractory population of severely obese individuals whose obesity may be driven by an MC4R pathway mutation in the absence of other clear history or clinical characteristics (1.4 times 95th percentile in children and adolescents aged 12 and older). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of individuals with POMC, LepR or PCSK1 genetic mutations |  | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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POMC, PCSK1, Pro-opiomelanocortin