RESUMEN
ST3GAL3 deficiency is an extremely rare autosomal recessive disorder caused by pathogenic mutations in the ST3GAL3 gene. Epilepsy, motor development delay, severe intellectual disability, and behavioral disorders have been reported to be associated with ST3GAL3 deficiency. In the present study, ST3GAL3 deficiency was caused by a homozygous splice-site mutation (NM_174964.4: c.936+1delG) in ST3GAL3. The patient described in this study was clinically similar to previously reported cases; nevertheless, we were able to detect repetitive behavior, previously not reported manifestations.
Asunto(s)
Epilepsia/genética , Discapacidad Intelectual/genética , Fenotipo , Sialiltransferasas/genética , Niño , Epilepsia/patología , Homocigoto , Humanos , Discapacidad Intelectual/patología , Masculino , Movimiento , Mutación , Sitios de Empalme de ARN , Sialiltransferasas/química , Conducta Estereotipada , SíndromeRESUMEN
Rett syndrome (RTT) is an X-linked severe neurological disorder. Mutations in Methyl-CpG-Binding Protein2 (MECP2) gene are the main cause of RTT disease. In this study, we report the results of screening the MECP2 gene for mutations in 7 Iranian patients with RTT syndrome. MECP2 sequencing identified two novel mutations in the heterozygous state, a splice mutation, c.354G>T, p.Gly119Gly, resulting in a premature splice-donor site and a 20-bp deletion, c.1167-1186del20 (p.P390Rfs), leading to modifying the c-terminal parts of the protein and it also changes the reading frames of all coding sequence downstream of the mutation. Multiple sequence alignment showed that amino acid changes occurred in the well conserved protein regions across species. Based on the results of this study and literature reviews, about 70% of mutations are found in exon 3 and 4 of the MECP2 gene, and mutations in exon 4 are more common than other exons. Therefore, it is recommended that exon 4 to be a priority for screening the genetic analysis of RTT patients.
Asunto(s)
Proteína 2 de Unión a Metil-CpG/genética , Mutación , Síndrome de Rett/genética , Secuencia de Aminoácidos , Niño , Exones , Femenino , Genotipo , Humanos , Irán , Masculino , Proteína 2 de Unión a Metil-CpG/química , Fenotipo , Homología de Secuencia de AminoácidoRESUMEN
BACKGROUND: Recurrent pregnancy loss (RPL) defined as three or more consecutive spontaneous miscarriages before the 20th week of gestation is caused by different factors including genetic and epigenetic background. However the involvement of paternal background on RPL is an interesting novel argument, which is not well studied. The main focus of the present study was to investigate for the association of paternal methylenetetrahydrofolate reductase (MTHFR) epigenotypes with sperm parameters and RPL. Moreover, the frequency of two of MTHFR Single Nucleotide Polymorphisms (SNPs) in males was assessed. METHODS: This is a case-control study. Methylation Specific PCR (MSP) was used to evaluate the methylation status of MTHFR promoter on sperm DNA of 25 male partners of RPL and 25 male partners of non-RPL couples. PCR-RFLP method was used to analyze 1,298 A>C (rs1801131) and 677 C>T (rs1801133) polymorphisms. RESULTS: No significant difference was observed in frequency of methylated MTHFR epigenotype between RPL and non-RPL males. Furthermore, methylated MTHFR epigenotype was more frequent (but not statistically significant) among men with abnormal sperm parameters compared to normal-sperm men. Among studied polymorphisms, only the mutated allele of C677T showed statistically higher prevalence among RPL males. CONCLUSIONS: Although our results do not establish any connection between MTHFR epigenotypes and RPL they do highlight the impact of C677T in the pathology.
