RESUMEN
PURPOSE: Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11-13, have recently been reported to cause Schaaf-Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties, and autism spectrum disorder. The causality of the reported variants in the context of the patients' phenotypes was questioned, as MAGEL2 whole-gene deletions seem to cause little or no clinical phenotype. METHODS: Here we report a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families, including 1 family with 3 individuals found to be affected with a truncating variant of MAGEL2, 11 individuals who are clinically affected but were not tested molecularly, and a presymptomatic fetal sibling carrying the pathogenic MAGEL2 variant. RESULTS: All cases harbor truncating mutations of MAGEL2, and nucleotides c.1990-1996 arise as a mutational hotspot, with 10 individuals and 1 fetus harboring a c.1996dupC (p.Q666fs) mutation and 2 fetuses harboring a c.1996delC (p.Q666fs) mutation. The phenotypic spectrum of Schaaf-Yang syndrome ranges from fetal akinesia to neurobehavioral disease and contractures of the small finger joints. CONCLUSION: This study provides strong evidence for the pathogenicity of truncating mutations of the paternal allele of MAGEL2, refines the associated clinical phenotypes, and highlights implications for genetic counseling for affected families.Genet Med 19 1, 45-52.
Asunto(s)
Trastorno del Espectro Autista/genética , Discapacidades del Desarrollo/genética , Discapacidad Intelectual/genética , Síndrome de Prader-Willi/genética , Proteínas/genética , Adolescente , Adulto , Trastorno del Espectro Autista/fisiopatología , Niño , Preescolar , Cromosomas Humanos Par 15 , Discapacidades del Desarrollo/fisiopatología , Femenino , Expresión Génica , Impresión Genómica , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/fisiopatología , Masculino , Mutación , Fenotipo , Síndrome de Prader-Willi/fisiopatologíaRESUMEN
PURPOSE: To identify the physical and psychosocial effects of equine-assisted activities and therapies (EAATs) on children with spinal muscular atrophy (SMA) from the perspective of the children and their parents. METHODS: The families of all eligible children with SMA, who reported participation in EAAT, from a Western metropolitan academic center were contacted and invited to participate. This study implemented qualitative, semistructured interviews of children with SMA and their parents. RESULTS: Three themes emerged from the qualitative content analysis: physical/psychosocial benefits; relationship development with the horses, instructors, and children; and barriers to continued EAAT engagement. CONCLUSIONS: The data suggest that the overall EAAT experience was a source of enjoyment, self-confidence, and normalcy for the children with SMA. The results of this study provide preliminary support for the use of EAAT among children with SMA.