RESUMO
Background: Escobar syndrome, a nonlethal variant of multiple pterygium syndromes (MPS), is a rare autosomal recessive disorder characterized by pterygia and multiple joint contractures along with other anomalies. Variants in cholinergic receptor nicotinic gamma subunit (CHRNG) have been previously reported in patients with Escobar syndrome. Objective: We studied a consanguineous Pakistani family affected with Escobar syndrome to identify the underlying genetic defect through short tandem repeat (STR) genotyping and direct DNA sequencing. Results: Genotyping with microsatellite markers (D2S427, D2S2344, and D2S206) revealed linkage of the disease phenotype in the family to the CHRNG locus. Using Sanger sequencing, we identified a homozygous nonsense CHRNG variant c.136C>T (p.R46*), predicted to produce a truncated protein that leads to acetylcholine receptor deficiency, causing MPS. The unaffected parents and siblings in the family were heterozygous carriers of this disease-causing variant. Conclusion: We report the identification of a nonsense CHRNG variant in a consanguineous Pakistani family affected with Escobar syndrome.
Assuntos
Anormalidades Múltiplas/genética , Códon sem Sentido , Hipertermia Maligna/genética , Receptores Nicotínicos/genética , Anormalidades da Pele/genética , Anormalidades Múltiplas/etnologia , Consanguinidade , Feminino , Genes Recessivos , Genótipo , Humanos , Masculino , Hipertermia Maligna/etnologia , Repetições de Microssatélites , Paquistão , Linhagem , Fenótipo , Receptores Nicotínicos/deficiência , Anormalidades da Pele/etnologiaRESUMO
BACKGROUND: Our primary objective was to detect malignant hyperthermia (MH)-susceptible persons and thereby prevent MH episodes. We identified variants in the ryanodine receptor isoform 1 using molecular pedigree analysis. METHODS: Nineteen exons covering major hotspots were chosen for the primary screening by polymerase chain reaction, denaturing high performance liquid chromatography, and confirmed by direct sequencing. RESULTS: Three novel variants involving amino acid changes were identified in two unrelated families as Met2698Arg, Glu2724Lys in exon 51 and Leu2785Val in exon 53. CONCLUSIONS: Three novel ryanodine receptor isoform 1 variants located either near or within the central domain might predispose carriers to MH.
Assuntos
Anestesia/efeitos adversos , Hipertermia Maligna/etiologia , Mutação , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Éxons , Predisposição Genética para Doença , Humanos , Masculino , Hipertermia Maligna/etnologia , Hipertermia Maligna/genética , Linhagem , Fenótipo , Medição de Risco , Fatores de Risco , TaiwanRESUMO
Eight Indian tribes from the Amazon region of Brazil (Araweté, Arara, Yamamadi, Kararaô, Karitiana, Waiampi, Surui and Cinta Larga) were studied for the distribution of the atypical and C5 variants of serum cholinesterase. None of them presented the CHE1*A allele, but the C5 variant was found in the Araweté (20.4%), Kararaô (15.6%), Karitiana (50.5%), Surui (12.3%) and Cinta Larga (19.6%) tribes. The frequency of the C5+ phenotype in the Karitiana is the highest reported thus far in human populations. Segregation studies considering the C5 variant were made among the Karitiana, and also among the Urubu-Kaapor and Munduruku tribes previously studied by Guerreiro et al [1987a, 1987b]. Most of the data were in agreement with the genetic hypothesis, but they also revealed a significant lack of the C5+ phenotype in offspring from C5+ X C5+ matings, as well as the occurrence of two C5+ children from C5- X C5- unions, in the Urubu-Kaapor tribe.
