Childrens Hospital Affiliated Capital Institute of Pediatrics

Beijing, China

Childrens Hospital Affiliated Capital Institute of Pediatrics

Beijing, China

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Yu-jin Q.,Capital Institute of Pediatrics | Juan D.,Capital Institute of Pediatrics | Er-zhen L.,Childrens Hospital Affiliated Capital Institute of Pediatrics | Jin-li B.,Capital Institute of Pediatrics | And 3 more authors.
BMC Medical Genetics | Year: 2012

Background: Proximal spinal muscular atrophy (SMA) is a common neuromuscular disorder resulting in death during childhood. Around 81 ~ 95% of SMA cases are a result of homozygous deletions of survival motor neuron gene 1 (SMN1) gene or gene conversions from SMN1 to SMN2. Less than 5% of cases showed rare subtle mutations in SMN1. Our aim was to identify subtle mutations in Chinese SMA patients carrying a single SMN1 copy.Methods: We examined 14 patients from 13 unrelated families. Multiplex ligation-dependent probe amplification analysis was carried out to determine the copy numbers of SMN1 and SMN2. Reverse transcription polymerase chain reaction (RT-PCR) and clone sequencing were used to detect subtle mutations in SMN1. SMN transcript levels were determined using quantitative RT-PCR.Results: Six subtle mutations (p.Ser8LysfsX23, p.Glu134Lys, p.Leu228X, p.Ser230Leu, p.Tyr277Cys, and p.Arg288Met) were identified in 12 patients. The p.Tyr277Cys mutation has not been reported previously. The p.Ser8LysfsX23, p.Leu228X, and p.Tyr277Cys mutations have only been reported in Chinese SMA patients and the first two mutations seem to be the common ones. Levels of full length SMN1 (fl-SMN1) transcripts were very low in patients carrying p.Ser8LysfsX23, p.Leu228X or p.Arg288Met compared with healthy carriers. In patients carrying p.Glu134Lys or p.Ser230Leu, levels of fl-SMN1 transcripts were reduced but not significant. The SMN1 transcript almost skipped exon 7 entirely in patients with the p.Arg288Met mutation.Conclusions: Our study reveals a distinct spectrum of subtle mutations in SMN1 of Chinese SMA patients from that of other ethnicities. The p.Arg288Met missense mutation possibly influences the correct splicing of exon 7 in SMN1. Mutation analysis of the SMN1 gene in Chinese patients may contribute to the identification of potential ethnic differences and enrich the SMN1 subtle mutation database. © 2012 Qu et al.; licensee BioMed Central Ltd.


Qu Y.-J.,Capital Institute of Pediatrics | Bai J.-L.,Capital Institute of Pediatrics | Cao Y.-Y.,Capital Institute of Pediatrics | Wang H.,Capital Institute of Pediatrics | And 7 more authors.
Journal of Molecular Diagnostics | Year: 2016

Proximal spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder caused by deletion or mutation of the survival of motor neuron 1 (SMN1). Here, we studied SMA molecular pathology in 653 Chinese patients and found approximately 88.2% with homozygous SMN1 exon 7 deletion and 6.3% with heterozygous exon 7 loss using multiplex ligation-dependent probe amplification. SMN1 variants were detected in 34 patients with heterozygous SMN1 loss by clone sequencing. In 27 of them, 15 variants were identified: five were unreported novel variants [c.-7_9del(p.0), p.Tyr109Cys, p.Ile249Tyrfs⋆16, p.Tyr272Trpfs⋆35, and c.835-5T>G], five were previously found only in Chinese patients (p.Ser8Lysfs⋆23, p.Gln14⋆, p.Val19Glyfs⋆21, p.Leu228⋆, and p.Tyr277Cys), and five were reported in other populations [p.Ala2Gly, p.Gln15⋆, p.Glu134Lys, p.Ser230Leu, and c.863G>T (r.835_⋆3del, p.Gly279Glufs⋆5)]. Variants p.Ser8Lysfs⋆23 and p.Leu228⋆ were the most common in Chinese SMA. Five variants (p.Ser8Lysfs⋆23, p.Gln14⋆, p.Gln15⋆, p.Val19Glyfs⋆21, and p.Leu228⋆) resulted in premature stop codons, likely causing SMN1 mRNA nonsense-mediated decay. The novel variant c.-7_9del (p.0) caused deletion of the translation start codon (AUG), resulting in full-length SMN protein loss. The novel variant c.835-5T>G, located in a splice site, resulted in 90% exon 7 skipping. Our study could facilitate early diagnosis for SMA patients in mutation detection and revealed the specific mutation spectrum of SMN1 in Chinese SMA and high genetic heterogeneity in subtle variants observed between patients from China and Caucasians. © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology


PubMed | Capital Institute of Pediatrics and Childrens Hospital Affiliated Capital Institute of Pediatrics
Type: Journal Article | Journal: The Journal of molecular diagnostics : JMD | Year: 2016

Proximal spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder caused by deletion or mutation of the survival of motor neuron 1 (SMN1). Here, we studied SMA molecular pathology in 653 Chinese patients and found approximately 88.2% with homozygous SMN1 exon 7 deletion and 6.3% with heterozygous exon 7 loss using multiplex ligation-dependent probe amplification. SMN1 variants were detected in 34 patients with heterozygous SMN1 loss by clone sequencing. In 27 of them, 15 variants were identified: five were unreported novel variants [c.-7_9del(p.0), p.Tyr109Cys, p.Ile249Tyrfs*16, p.Tyr272Trpfs*35, and c.835-5T>G], five were previously found only in Chinese patients (p.Ser8Lysfs*23, p.Gln14*, p.Val19Glyfs*21, p.Leu228*, and p.Tyr277Cys), and five were reported in other populations [p.Ala2Gly, p.Gln15*, p.Glu134Lys, p.Ser230Leu, and c.863G>T (r.835_*3del, p.Gly279Glufs*5)]. Variants p.Ser8Lysfs*23 and p.Leu228* were the most common in Chinese SMA. Five variants (p.Ser8Lysfs*23, p.Gln14*, p.Gln15*, p.Val19Glyfs*21, and p.Leu228*) resulted in premature stop codons, likely causing SMN1 mRNA nonsense-mediated decay. The novel variant c.-7_9del (p.0) caused deletion of the translation start codon (AUG), resulting in full-length SMN protein loss. The novel variant c.835-5T>G, located in a splice site, resulted in 90% exon 7 skipping. Our study could facilitate early diagnosis for SMA patients in mutation detection and revealed the specific mutation spectrum ofSMN1 in Chinese SMA and high genetic heterogeneity in subtle variants observed between patients from China and Caucasians.


PubMed | Childrens Hospital Affiliated Capital Institute of Pediatrics
Type: Comparative Study | Journal: Rheumatology international | Year: 2013

The objective of this study was to determine how the clinical presentation of systemic lupus erythematosus in pediatric varied with the age of onset of the disease. We reviewed the charts of a total of 88 Chinese pediatric patients (pSLE) diagnosed and admitted first time to our hospitals between 2005 and 2008. Patients were divided into 3 groups, depending on the age at diagnosis: preschool (1-6 years), school age (7-11 years), and adolescent groups (12-18 years). Among the three groups, we compared the sex ratio, disease duration at diagnosis, symptoms at the onset of the disease, clinical manifestations, laboratory examinations, SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) 2000, and SLICC/ACR SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus). Most pediatric patients were in the adolescent group (47.7%), while the disease duration at diagnosis was shortest in preschool-age patients (0.65 0.5 months). The most common symptoms at the onset of pSLE were fever, rash, arthritis, and seizures. Hematologic system and neuropsychiatric system were damaged commonly. The preschool-age patients had the shortest disease duration at diagnosis, the highest incidence of neuropsychiatric system involvement, and the poorest prognosis of all the age groups, especially the boys. Patients in adolescence had the peak incidence of pediatric SLE and high disease activity, begins to acquire some of the adult characteristics. School-age is a transition stage between other stages.

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