Objective To investigate the clinical and genetic characteristics of spinal muscular atrophy(SMA)patients with SMNI gene compound heterozygous mutations.Methods Three SMA-II pedigrees treated in Henan Provincial Peopl...Objective To investigate the clinical and genetic characteristics of spinal muscular atrophy(SMA)patients with SMNI gene compound heterozygous mutations.Methods Three SMA-II pedigrees treated in Henan Provincial People's Hospital from October 2019 to July 2020 were selected.The clinical data of 3 SMA-II probands were retrospectively analyzed.Multiplex ligationdependent probe amplification(MLPA)technology was used to detect the copy number of the SMN gene in the probands and their parents.Polymerase chain reaction amplification combined with microfluidic capillary electrophoresis were used to detect point mutations in the SMNI gene of the probands.Sanger sequencing was used to validate candidate variant sites.Results The 3 probands are all male,aged 19,17 and 12 years,respectively.The main clinical manifestations were symmetrical muscle weakness mainly in the proximal lower limbs,mild to moderate elevation of serum creatine kinase,and neurogenic injury as determined by electromyography or muscle pathology.The genetic testing results showed that all 3 probands had heterozygous deletion in exon 7 of the SMNI gene,and carried heterozygous variations c.275G>A(p.Trp92),c.689C>T(p.Ser230Leu),and c.708dupT(p.Pro237Serfs 19),respectively.The exon deletion and point mutation were inherited separately from their parents.c.275G>A(p.Trp92)and c.708dupT(p.Pro237Serfs 19)variations had not been reported before.Conclusion The clinical manifestations of SMAII patients are symmetrical muscle weakness,mainly in the proximal extremities of both lower limbs,and electromyography or muscle biopsy suggesting neurogenic lesions.The compound heterozygous variation of point mutation and heterozygous deletion in the SMNI gene can lead to SMA-II.Suspected SMA patients with SMNI gene heterozygous deletion should take point mutation testing.展开更多
文摘Objective To investigate the clinical and genetic characteristics of spinal muscular atrophy(SMA)patients with SMNI gene compound heterozygous mutations.Methods Three SMA-II pedigrees treated in Henan Provincial People's Hospital from October 2019 to July 2020 were selected.The clinical data of 3 SMA-II probands were retrospectively analyzed.Multiplex ligationdependent probe amplification(MLPA)technology was used to detect the copy number of the SMN gene in the probands and their parents.Polymerase chain reaction amplification combined with microfluidic capillary electrophoresis were used to detect point mutations in the SMNI gene of the probands.Sanger sequencing was used to validate candidate variant sites.Results The 3 probands are all male,aged 19,17 and 12 years,respectively.The main clinical manifestations were symmetrical muscle weakness mainly in the proximal lower limbs,mild to moderate elevation of serum creatine kinase,and neurogenic injury as determined by electromyography or muscle pathology.The genetic testing results showed that all 3 probands had heterozygous deletion in exon 7 of the SMNI gene,and carried heterozygous variations c.275G>A(p.Trp92),c.689C>T(p.Ser230Leu),and c.708dupT(p.Pro237Serfs 19),respectively.The exon deletion and point mutation were inherited separately from their parents.c.275G>A(p.Trp92)and c.708dupT(p.Pro237Serfs 19)variations had not been reported before.Conclusion The clinical manifestations of SMAII patients are symmetrical muscle weakness,mainly in the proximal extremities of both lower limbs,and electromyography or muscle biopsy suggesting neurogenic lesions.The compound heterozygous variation of point mutation and heterozygous deletion in the SMNI gene can lead to SMA-II.Suspected SMA patients with SMNI gene heterozygous deletion should take point mutation testing.
