| Objective: To better understand the clinical course and prognosis of infantile-onset Pompe disease(IOPD)in China’s mainland,we analyze the clinical data and explore the molecular genetic characterizations of IOPD patients in Shanghai Children’s Medical Center.In this way,we provide evidences of early diagnosis,reasonable treatment,molecular diagnosis and genetic counseling of IOPD.Methods: Twenty-five Chinese patients with IOPD diagnosed by Shanghai Children’s Medical Center from 2013 to 2016 were enrolled in this study.Their clinical data of initial presentation,sign,laboratory tests and auxiliary examinations,such as X-ray,electrocardiogram and heart ultrasound,were retropspectively reviewed.Their motor development,child survival and other follow-up data were evaluated.Peripheral blood(2ml)was collected from all the individuals and genomic DNA was extracted using a commercial kit..All coding exons(e2-20)and intron/exon boundaries of the GAA gene were amplified by polymerase chain reaction using primers with 16 pairs of primers.The PCR products were analyzed by forward and reverse sequencing.The resulting DNA was sequenced analyzed using the forward and reverse primers.All the mutations were sequence analyzed with their parents.Each novel mutation was screened in 60 normal individuals using direct sequencing.Results: A total of 25 unrelated patients(14 males and 11 females)were diagnosed with IOPD in our institution based on the clinical presentations,GAA enzyme activity assay and gene testing.23(92%)patients had shortened P-R interval performance.All the 25 children were complicated with cardiac hypertrophy,and the left ventricular mass index(LVMI)was 133-575g/m2.A total of 30 different mutations were identified in this study,and 13 of which were novel.Two hot spots were found in children with IPOD.Nonsense mutation c.2662G> T(p.Glu888X)is the most common mutation identified in this study.This mutant allele accounts for an average of 14% of total mutant alleles detected in this group.The missense mutation c.1935C>A(p.Asp645Glu)was the next most common mutation identified in this study.This mutant allele accounts for an average of 12% of total mutant alleles detected in this group.Conclusion: IOPD is a progressive and often fatal disease.Hypertrophic cardiomyopathy,hypotonia,muscle weakness were reported as frequently presenting signs and symptoms in patients with IOPD.We found 13 new mutations and 2 hotspots in 25 patients with IOPD in China’s mainland.c.2662G> T is the most common mutation in children with IPOD in northern China,whereas c.1935C> A is the most common mutation in children with IPOD in southern China. |
