[Genetic tests and clinical re-evaluation of 85 children with suspected spinal muscular atrophy].
OBJECTIVE
Spinal muscular atrophy (SMA), characterized by degeneration of the anterior horn cells in the spinal cord and symmetric proximal muscle weakness, is the most common autosomal recessive neuromuscular disease in infants and children. In Caucasian population, about 95% of clinically typical patients lack both copies of the telomeric survival motor neuron gene (SMN 1). However, the detection rate of the homozygous absence in Chinese patients is still controversial, which may lead to reduced confidence in the SMA genetic testing in clinical practice. The purpose of the current study was to determine the frequency of homozygous deletions of SMN 1 in Chinese patients, to evaluate the significance of the SMN 1 homozygous deletion assay in clinical applications, and the impact of the clinical re-visit followed by the genetic testing.


METHODS
Totally 85 patients initially suspected of SMA were referred for SMA genetic testing. A polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay was used to detect the homozygous absence of SMN 1. Clinical re-visit was performed by the pediatric neurology specialists according to the international SMA diagnostic criteria, and histological examinations were carried out when they were necessary.


RESULTS
Absence of both copies of SMN 1 exon 7 were found in 57 (67%) of the 85 patients, and 28 patients (33%) had at least one copy. For the 28 patients with negative results, 19 were followed up by the pediatric neurologists. The clinical diagnosis of SMA could be excluded in 15 patients, but retained in the other 4 patients after the clinical re-evaluation and histological examinations. Thus, approximately 95% of the patients with clinically typical SMA in our cohort lacked both copies of SMN 1. Homozygous deletions of SMN 1 were detected in 96% (22/23), 93% (28/30) and 100% (7/7) of the patients with SMA type I, type II and type III, respectively. There was no significant difference in the deletion frequency among the subtypes.


CONCLUSIONS
The frequency of homozygous deletions of SMN 1 in this series of Chinese SMA patients was about 95%, which is similar to that reported in Caucasian population. The genetic test of homozygous deletions of SMN 1 should be considered as the first line test for the Chinese patients suspected of SMA. The clinical re-visit and re-evaluation which is essential in clinical diagnosis, genetic counseling and medical management, should be routinely performed after the genetic testing.
Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Xing
X
Ji
Xiao-qing
XQ
Liu
Jia-wei
JW
Shen
Xi-hua
XH
Li
Jiong
J
Tao
D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
D055533:Survival of Motor Neuron 1 Protein