Obesidad monogénica y sindrómica
La heredabilidad de la obesidad se estima entre el 40 y el 70%, pero la genética de la obesidad para la mayoría de los individuos es compleja e implica la interacción de múltiples genes con el medio ambiente.
Descripción general
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La heredabilidad de la obesidad se estima entre el 40 y el 70%, pero la genética de la obesidad para la mayoría de los individuos es compleja e implica la interacción de múltiples genes con el medio ambiente. Sin embargo, existen varias formas sindrómicas y no sindrómicas de obesidad que son monogénicas y oligogénicas que proporcionan información sobre el control molecular subyacente de la ingesta de alimentos y los mecanismos que controlan el comportamiento ingestivo y la saciedad para regular el peso corporal. El modo de herencia suele ser autosómico dominante.
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El panel de precisión monogénico y sindrómico de Igenomix se puede utilizar para realizar un diagnóstico diferencial directo y preciso de la obesidad, lo que en última instancia conduce a un mejor manejo y pronóstico de la enfermedad y sus resultados. Proporciona un análisis completo de los genes involucrados en esta enfermedad utilizando secuenciación de próxima generación (NGS) para comprender completamente el espectro de genes relevantes involucrados.
Indicaciones
El panel de precisión de obesidad monogénica y sindrómica de Igenomix está indicado para aquellos pacientes con obesidad con o sin antecedentes familiares de obesidad que presenten las siguientes manifestaciones:
- Patrón de crecimiento de peso anormal
- Índice de masa corporal elevado
- Hipertensión
- Diabetes tipo 2
- Síndrome metabólico
Utilidad clínica
La utilidad clínica de este panel es:
- La confirmación genética y molecular para un diagnóstico clínico preciso de un paciente sintomático.
- Inicio temprano del tratamiento con un equipo multidisciplinario para terapia farmacológica temprana, intervención quirúrgica y / o modificaciones dietéticas para reducir las comorbilidades asociadas con la obesidad.
- Evaluación de riesgo de familiares asintomáticos según el modo de herencia.
Genes y enfermedades
Ver todos los genes y enfermedades
| GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
| ADCY3 | Body Mass Index Quantitative Trait Locus | AR | 97.98% | 7 of 7 |
| AFF4 | Chops Syndrome, Cognitive Impairment-Coarse Facies-Heart Defects-Obesity-Pulmonary Involvement-Short Stature-Skeletal Dysplasia Syndrome | AD | 99.42% | 6 of 6 |
| ALMS1 | Alstrom Syndrome | AR | 99.92% | 302 of 305 |
| ARL6 | Bardet-Biedl Syndrome, Retinitis Pigmentosa | AD,AR,X,XR,G | 100% | 17 of 21 |
| BBIP1 | Bardet-Biedl Syndrome | AR | 99.88% | 1 of 1 |
| BBS1 | Bardet-Biedl Syndrome | AR | 100% | 102 of 105 |
| BBS10 | Bardet-Biedl Syndrome | AR | 100% | 114 of 114 |
| BBS12 | Bardet-Biedl Syndrome | AR | 99.78% | 61 of 61 |
| BBS2 | Bardet-Biedl Syndrome, Retinitis Pigmentosa | AR | 100% | 99 of 100 |
| BBS4 | Bardet-Biedl Syndrome | AR | 100% | 45 of 48 |
| BBS5 | Bardet-Biedl Syndrome | AR | 99.80% | 30 of 31 |
| BBS7 | Bardet-Biedl Syndrome | AR | 100% | 48 of 48 |
| BBS9 | Bardet-Biedl Syndrome | AR | 99.56% | 50 of 51 |
| C8ORF37 | Bardet-Biedl Syndrome, Cone Rod Dystrophy, Retinitis Pigmentosa | AD,AR,X,XR,G | na | na |
| CEP19 | Morbid Obesity And Spermatogenic Failure | AR | 99.88% | 2 of 2 |
| CEP290 | Bardet-Biedl Syndrome, Joubert Syndrome, Joubert Syndrome With Oculorenal Defect, Leber Congenital Amaurosis, Meckel Syndrome, Senior-Loken Syndrome | AR | 96.47% | 293 of 327 |
| CUL4B | X-Linked Mental Retardation With Short Stature, Small Testes, Musclewasting, And Tremor, X-linked Intellectual Disability, Cabezas Type | X,XR,G | 99.77% | NA of NA |
| DYRK1B | Abdominal Obesity-Metabolic Syndrome | AD | 99.72% | 3 of 3 |
| GNAS | ACTH-Independent Macronodular Adrenal Hyperplasia, Albright Hereditary Osteodystrophy, Cushing Syndrome, Mazabraud Syndrome, McCune-Albright Syndrome, Progressive Osseous Heteroplasia, Pseudohypoparathyroidism Type 1A Pseudohypoparathyroidism Type 1B, Pseudohypoparathyroidism Type 1C, Pseudopseudohypoparathyroidism | AD | 99.95% | 263 of 273 |
| IFT172 | Bardet-Biedl Syndrome, Jeune Syndrome, Retinitis Pigmentosa, Short-Rib Thoracic Dysplasia | AR | 100% | 37 of 37 |
| IFT27 | Bardet-Biedl Syndrome | AR | 100% | 5 of 5 |
| IFT74 | Bardet-Biedl Syndrome | AR | 99.95% | 6 of 6 |
| KIDINS220 | Spastic Paraplegia-Intellectual Disability-Nystagmus-Obesity Syndrome | AD | 99.83% | 17 of 17 |
| KSR2 | Obesity, Insulin Resistance and Impaired Cellular Fuel Oxidation | 99.88% | 29 of 29 | |
| LEP | Leptin Deficiency Or Dysfunction | AR | 100% | 19 of 19 |
| LEPR | Leptin Receptor Deficiency | AR | 97.92% | 49 of 49 |
| LZTFL1 | Bardet-Biedl Syndrome | AR | 99.83% | 4 of 4 |
| MAGEL2 | MAGEL2-related Prader-Willi-Like Syndrome, Prader-Willi Syndrome | AD | 99.99% | 43 of 48 |
| MC4R | Body Mass Index Quantitative Trait Locus, Obesity Due To Melanocortin 4 Receptor Deficiency | AD,AR | 100% | 165 of 166 |
| MKKS | Bardet-Biedl Syndrome, Mckusick-Kaufman Syndrome | AR | 89.96% | 71 of 71 |
| MKS1 | Bardet-Biedl Syndrome, Joubert Syndrome, Joubert Syndrome With Ocular Defect, Meckel Syndrome | AR | 99.98% | 49 of 49 |
| MYT1L | Autosomal Dominant Mental Retardation, MRD39 chromosome 2p25.3 Deletion Syndrome | AD | 99.98% | 30 of 30 |
| NR0B2 | Obesity | AD,AR,MU,P | 99.09% | 15 of 15 |
| NTRK2 | Early Infantile Epileptic Encephalopathy, Obesity, Hyperphagia, And Developmental Delay, Undetermined Early-onset Epileptic Encephalopathy, West Syndrome | AD | 100% | 9 of 9 |
| PCSK1 | Obesity Due To Prohormone Convertase I Deficiency, Proprotein Convertase 1 Deficiency | AR | 99.98% | 45 of 45 |
| PHF6 | Borjeson-Forssman-Lehmann Syndrome | X,XR,G | 99.93% | NA of NA |
| PHIP | Developmental Delay, Intellectual Disability, Obesity, And Dysmorphic Features | AD | 98.74% | 51 of 52 |
| POMC | Obesity Due To Pro-Opiomelanocortin Deficiency | AD,AR,MU,P | 99.98% | 40 of 40 |
| PPARG | Berardinelli-Seip Congenital Lipodystrophy, Carotid Intimal Medial Thickness, Noninsulin-Dependent Diabetes Mellitus, Familial Partial Lipodystrophy, Obesity, PPARG-related Familial Partial Lipodystrophy | AD,AR,MU,P | 99.94% | 53 of 53 |
| PRMT7 | Short Stature-Brachydactyly-Obesity-Global Developmental Delay Syndrome | AR | 100% | 13 of 14 |
| RAI1 | 17p11.2 Microduplication Syndrome, PMP22-RAI1 Contiguous Gene Duplication Syndrome, Smith-Magenis Syndrome | AD | 99.91% | 50 of 53 |
| SDCCAG8 | Bardet-Biedl Syndrome, Senior-Loken Syndrome | AR | 96.29% | 18 of 19 |
| SETD2 | Luscan-Lumish Syndrome, Sotos Syndrome | AD | 99.83% | 19 of 19 |
| SH2B1 | Distal 16p11.2 Microdeletion Syndrome, Proximal 16p11.2 Microdeletion Syndrome, Severe Early-Onset Obesity-Insulin Resistance Syndrome Due To Sh2b1 Deficiency | 99.98% | 25 of 25 | |
| SIM1 | 6q16 Microdeletion Syndrome, Obesity Due To SIM1 Deficiency, SIM1-Related Prader-Willi-Like Syndrome | 99.64% | 39 of 40 | |
| TRIM32 | Bardet-Biedl Syndrome, Limb-Girdle Muscular Dystrophy Type 2H, TRIM32-Related Limb-Girdle Muscular Dystrophy | AR | 100% | 17 of 17 |
| TTC8 | Bardet-Biedl Syndrome, Retinitis Pigmentosa | AR | 99.33% | 28 of 28 |
| UCP3 | Obesity | AD,AR,MU,P | 99.98% | 6 of 6 |
| VPS13B | Cohen Syndrome | AR | 99.98% | 182 of 190 |
| WDPCP | Bardet-Biedl Syndrome, Congenital Heart Defects, Hamartomas Of Tongue, And Polysyndactyly, Meckel Syndrome | AR | 99.30% | 8 of 8 |
* Herencia: AD: Autosómico Dominante; AR: autosómico recesivo; X: ligado a X; XLR: recesivo vinculado a X; Mi: mitocondrial; Mu: multifactorial; G: herencia gonosomal; D: herencia digénica
** HGMD: número de mutaciones clínicamente relevantes según HGMD
Referencias
Rohde, K., Keller, M., la Cour Poulsen, L., Blüher, M., Kovacs, P., & Böttcher, Y. (2019). Genetics and epigenetics in obesity. Metabolism: clinical and experimental, 92, 37–50. https://doi.org/10.1016/j.metabol.2018.10.007
Reddon, H., Guéant, J. L., & Meyre, D. (2016). The importance of gene-environment interactions in human obesity. Clinical science (London, England : 1979), 130(18), 1571–1597. https://doi.org/10.1042/CS20160221
Kleinberger, J. W., Copeland, K. C., Gandica, R. G., Haymond, M. W., Levitsky, L. L., Linder, B., Shuldiner, A. R., Tollefsen, S., White, N. H., & Pollin, T. I. (2018). Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genetics in medicine : official journal of the American College of Medical Genetics, 20(6), 583–590. https://doi.org/10.1038/gim.2017.15
