Human SMN1/DMD/FMR1 Mutation Detection Kit

Duchenne muscular dystrophy (DMD) represents the most common X-linked recessive neuromuscular disease, affecting approximately 1 in 3,500 live male births, with little geographical or ethnic differences. A substantial proportion of affected individuals exhibit familial aggregation; however, about one-third of cases arise from de novo mutations. The primary cause of DMD is a mutation in the DMD gene, with deletions being the most frequent form, accounting for 55%-65% of all cases, predominantly involving exons 44-55 and 2-19. Duplications contribute to 5%-15% of cases, whereas point mutations account for around 30%.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of anterior horn cells of the spinal cord that leads to muscle weakness and atrophy. The incidence is approximately 1 in 6,000 to 1 in 10,000 live births, and carrier frequencies are estimated at 1 in 40 to 1 in 50, making it the second cause among childhood fatal autosomal recessive disorders. The 90-95% of individuals affected by SMA is caused by homozygous deletion of the survival motor neuron 1(SMN1) gene; the remaining 3-5% results from compound heterozygous deletion / point mutation (or partial deletion) in the SMN1 gene. The survival motor neuron 2 (SMN2) gene produces 10-20% of full-length functional transcripts. A higher number of SMN2 copies closely correlates with milder clinical phenotype in SMA patients.

Fragile X syndrome (FXS) is the most common X-linked recessive monogenic intellectual disability syndrome, accounting for 15%–25% of all X-linked intellectual disability disorders, with its prevalence after trisomy 21 (Down syndrome). Over 99% of FXS cases are caused by expansion and hypermethylation of the CGG trinucleotide repeat sequence (CGG)n in the FMR1 gene. Full mutations (n>200) occur predominantly in males, with an incidence of 1 in 4,000–6,000 males and 1 in 8,000 females. Males and some of females affected with full mutations suffer from severe intellectual disability and self-care deficit, which is incurable and a heavy familial and social burden. Premutations (n=55–200) of the FMR1 gene are associated with diminished ovarian reserve, recurrent miscarriage, premature ovarian insufficiency, infertility, and IVF failure in females, as well as tremor/ataxia syndrome in males during adulthood. The 55x CGG repeat is a dividing line. Individuals with repeat size less than 55 typically have normal phenotypes and low risk of passing on mutations to offsprings. Individuals with repeat size greater than 55 are premutation / full mutation carriers or patients, and more likely transmit a larger repeat size including a full mutation to offsprings, thereby producing more severe clinical phenotypes.

The three genetic conditions above have high incidences, mortality rates and disability rates. No curative treatments are available and medical costs are expensive. However, these conditions can be mitigated by genetic screening for couples who are planning a pregnancy or are pregnant to prevent most of the birth of a child affected by a specific one. The American College of Obstetricians and Gynecologists (ACOG) has issued an expert consensus on "Carrier Screening in the Age of Genomic Medicine" that strongly recommends screening for fragile X syndrome and spinal muscular atrophy for all couples who are planning a pregnancy or are pregnant.