RESUMO
Myotonia congenita is an inherited muscle disorder caused by mutations in the CLCN1 gene, a voltage-gated chloride channel of skeletal muscle. We have studied 48 families with myotonia, 32 out of them carrying mutations in CLCN1 gene and eight carry mutations in SCN4A gene. We have found 26 different mutations in CLCN1 gene, including 13 not reported previously. Among those 26 mutations, c.180+3A>T in intron 1 is present in nearly one half of the Spanish families in this series, the largest one analyzed in Spain so far. Although scarce data have been published on the frequency of mutation c.180+3A>T in other populations, our data suggest that this mutation is more frequent in Spain than in other European populations. In addition, expression in HEK293 cells of the new missense mutants Tyr137Asp, Gly230Val, Gly233Val, Tyr302His, Gly416Glu, Arg421Cys, Asn567Lys and Gln788Pro, demonstrated that these DNA variants are disease-causing mutations that abrogate chloride currents.
Assuntos
Canais de Cloreto/genética , Saúde da Família , Testes Genéticos/métodos , Mutação/genética , Miotonia/diagnóstico , Miotonia/genética , Adolescente , Adulto , Fenômenos Biofísicos/genética , Biofísica , Linhagem Celular Transformada , Criança , Estimulação Elétrica , Eletromiografia , Feminino , Humanos , Masculino , Potenciais da Membrana/genética , Pessoa de Meia-Idade , Mutagênese Sítio-Dirigida , Técnicas de Patch-Clamp , Espanha , Transfecção , Adulto JovemRESUMO
We identified a deletion of a gene encoding a subunit of RNA polymerases I and III, POLR1D, in an individual with Treacher Collins syndrome (TCS). Subsequently, we detected 20 additional heterozygous mutations of POLR1D in 252 individuals with TCS. Furthermore, we discovered mutations in both alleles of POLR1C in three individuals with TCS. These findings identify two additional genes involved in TCS, confirm the genetic heterogeneity of TCS and support the hypothesis that TCS is a ribosomopathy.
Assuntos
Disostose Mandibulofacial/genética , Mutação , RNA Polimerase III/genética , RNA Polimerase I/genética , Adulto , Alelos , Criança , Pré-Escolar , Feminino , Heterogeneidade Genética , Humanos , Masculino , Disostose Mandibulofacial/enzimologia , Fenótipo , Subunidades Proteicas/genéticaRESUMO
OBJECTIVE: To report a case of nonidentical twins affected with a congenital form of Steinert's myotonic dystrophy (DM1), conceived by IVF owing to parental sterility, in which the mother presented a paucisymptomatic form of DM1 which was diagnosed as a result of the condition inherited by the twins. DESIGN: Case report. SETTING: Neonatal intensive care unit of a tertiary hospital. PATIENT(S): Newborn twins affected with the congenital form of DM1 and a 35-year-old nulliparous mother. INTERVENTION(S): In vitro fertilization. MAIN OUTCOME MEASURE(S): Molecular study of the CTG triplet expansion related with DM1. RESULT(S): Molecular study evidenced a pathologic expansion in both twins as well as in their mother. CONCLUSION(S): This case should serve as a reminder to practitioners that assisted reproductive techniques have opened the possibility that asymptomatic or paucisymptomatic carriers of a genetic syndrome can inadvertently conceive fetuses affected with more serious forms of the illness.