Compound heterozygous mutation in two unrelated cases of Chinese XXXX @entity1 .

@entity1 @entity23247 @entity74 @entity23997 @entity11280 @entity2057 @entity72940 @entity72939
BACKGROUND: Infantile proximal @entity2057 ( @entity2057 ) is a common @entity74 . Approximately 90% - 95% cases of @entity2057 result from homozygous deletion of @entity11280 ( @entity11280 ) and 5% cases are caused by compound heterozygous mutation (a @entity11280 deletion on one allele and a subtle mutation on the other allele). METHODS: In this research, two unrelated @entity1 were clinically diagnosed according to the criteria of proximal @entity2057 . Genetic diagnosis was performed to detect the homozygous deletion of exon 7 of @entity11280 by PCR-restriction fragment length polymorphism (RFLP) and genomic sequencing. Multiplex ligation-dependent probe amplification (MLPA) analysis was carried out to measure copy numbers of @entity11280 , @entity23247 and @entity23997 ( @entity23997 ) in the @entity1 . Further sequencing of @entity11280 allele-specific PCR (AS-PCR) and @entity11280 clones were also performed to analyze the point mutation of @entity11280 gene. Additionally, the pedigree analysis of these two families was carried out to identify the transmission of the mutation. RESULTS: The inconsistent results using PCR-RFLP and genomic sequencing showed homozygous deletion of exon 7 of @entity11280 and heterozygous deletion accompanied with a suspicious mutation in @entity11280 gene, respectively. MLPA analysis of these two cases exhibited one @entity11280 copy deletion. One identical @entity72939 ( @entity72940 ) mutation was found in two cases by sequencing the @entity11280 clones, which confirmed that both cases were @entity2057 compound heterozygotes. One case showed partial conversion to form hybrid SMN ( @entity23247 I7/ @entity11280 E8) identified by clones sequencing and another case carrying 3 @entity23247 implied complete conversion from @entity11280 to @entity23247 . CONCLUSION: @entity72940 is more a disease-causing mutation than a polymorphism variation, and @entity1 with this mutation may have more severe phenotypes.
