Abstract
Background Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease, which is caused by mutations of the survival motor neuron 1 (SMN1) gene. At present, the gene therapy medicine for SMA, i.e. , Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. In this study, we analyzed the deletion of SMN gene in patients suspected of SMA, and performed prenatal genetic diagnosis of SMA. Methods In this study, we collected the peripheral blood of 419 probands and their parents who were treated in the genetic counseling clinic at our hospital from January 2010 to September 2019, and extracted DNA from the blood samples for analysis. Patients who were diagnosed with SMA were first tested by MLPA. The patients with negative MLPA results were further analysed with long-range PCR combined with nest PCR and validated by Sanger sequencing to look for point mutations. In 293 families, pregnant women were subjected to chorionic villus or amniotic fluid sampling for prenatal genetic diagnosis depending on gestational weeks. In addition to the above methods used for genetic diagnosis, we also used QF-PCR in all prenatal diagnoses, which can help detect the presence of trisomy of chromosome while eliminating maternal contamination. Results 1. Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). 2. In total, 10 point mutations were detected in the 15 pedigrees. Five of these variants have not been previously reported in the literature. 3. Among the 293 pedigrees that underwent one prenatal diagnosis, 118 foetuses were normal, 149 foetuses were carriers of heterozygous variants, and the remaining 72 foetuses harboured compound heterozygous variants or homozygous variants. 4. In all prenatal diagnoses, we found one 21-trisomy fetus by QF-PCR. Couples whose foetuses were normal or carriers continued the pregnancy, whereas couples whose foetuses harboured compound heterozygous variants or homozygous variants decided to terminate the pregnancy. The follow-up results were consistent with the prenatal diagnosis.
Prenatal diagnosis of Fraser syndrome caused by novel variants of FREM2
