ABSTRACT
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.
Subject(s)
Muscular Atrophy, Spinal/diagnosis , Muscular Atrophy, Spinal/genetics , Mutation , Survival of Motor Neuron 1 Protein/genetics , Computational Biology/methods , Exons , Female , Gene Dosage , Genotype , Humans , Male , Phenotype , RNA Splicing , RNA, Messenger/genetics , Sequence Deletion , Transcription, GeneticABSTRACT
BACKGROUND: Intrapulmonary lipoma is extemely rare in children. So far, all reported pulmonary lipomas were from adult patients. METHODS: We present herein a case of intrapulmonary lipoma in a child and a review of the related literature. RESULTS: A 13-month-old boy was hospitalized because of cough and fever. Chest CT showed patchy infiltration and round-shape, hypodense homogeneous lesions located in the lung. After 19 days of antibiotic treatment, his clinic symptoms disappeared, but the round lesions remained without any change. One month and one year later, he was examined by chest MRI with technique of fat suppression. The child was diagnosed as having an intrapulmonary lipoma without biopsy. CONCLUSIONS: Intrapulmonary lipoma is rare in children. Chest CT and MRI are very important for the correct diagnosis of intrapulmonary lipoma.
Subject(s)
Lipoma/diagnosis , Lung Neoplasms/diagnosis , Diagnosis, Differential , Humans , Infant , MaleABSTRACT
We evaluated survival motor neuron 2 (SMN2) and neuronal apoptosis inhibitory protein (NAIP) gene copy distribution and the association of copy number with survival in 232 Chinese spinal muscular atrophy (SMA) patients. The SMN2 and NAIP copy numbers correlated positively with the median onset age (r = 0.72 and 0.377). The risk of death for patients with fewer copies of SMN2 or NAIP was much higher than for those with more copies (P < .01). The survival probabilities at 5 years were 5.1%, 90.7%, and 100% for 2, 3, and 4 SMN2 copies and 27.9%, 66.7%, and 87.2% for 0, 1, and 2 NAIP copies, respectively. Our results indicated that combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age and poorer survival probability. Better survival status for Chinese type I SMA might due to a higher proportion of 3 SMN2 and a lower rate of zero NAIP.
Subject(s)
DNA Copy Number Variations , Muscular Atrophy, Spinal/genetics , Neuronal Apoptosis-Inhibitory Protein/genetics , Age of Onset , Asian People/genetics , Child, Preschool , China , Cohort Studies , Humans , Infant , Infant, Newborn , Muscular Atrophy, Spinal/epidemiology , Survival Analysis , Survival of Motor Neuron 2 Protein/geneticsABSTRACT
OBJECTIVE: To investigate the type and frequency of gene conversion from SMN1 to SMN2 in Chinese patients affected with spinal muscular atrophy (SMA), and to explore the relationship between gene conversion and clinical phenotype. METHODS: Non-homozygous deletion of SMN1 gene exon 8 was screened among 417 patients with SMN1 exon 7 homozygous deletions. To analyze and verify the types of gene conversion, genomic DNA sequencing, multiplex ligation-dependent probe amplification (MLPA), and gene subcloning and sequencing were carried out. RESULTS: Thirty-one patients (7.4% of all) with non-homozygous deletions of SMN1 exon 8 were detected. Through series of experiments, the fusion genes SMN1/SMN2 in all cases were delineated. Five types of gene conversions were identified, which included SMN2-I7b/SMN1 E8, SMN2-I7a/SMN1 I7b, SMN2-E7/SMN1 I7a, SMN1 I6/SMN2 E7/SMN1 I7a and SMN2-E7/SMN1 I7a/SMN2 I7b. Such conversions were found in the type I-III patients. For 10 patients with type I-III SMA and 3 copies of SMN2 gene produced by conversion, the average survival age was 5 year and 4 months. CONCLUSION: Partial conversions of SMN1 gene have been found among Chinese SMA patients. The type of conversion and frequency seem to be different from those of other races. Gene conversion to some extent may impact on survival time and rate of SMA patients, especially type I SMA.