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1.
Albena Jordanova Violeta Stoyanova Maria Uzunova Ivan Litvinenko Ivo Kremensky 《Human mutation》1998,12(1):33-38
All three types of autosomal recessive spinal muscular atrophy map to chromosome region 5q13. Recent reports suggest that they are associated with deletions of two adjacent genes: SMN and NAIP. Here we report the first deletion analysis of Bulgarian SMA families. Homozygous deletion of exons 7 and 8 of the SMN gene were found in 85% of our patients, but the NAIP gene (exons 5 and 6) was deleted in only 26% of patients. To our knowledge, these frequencies are some of the lowest reported so far. The NAIP gene was deleted predominantly in severely affected patients (type I), while in the group with milder types SMA only deletions of the SMN gene were detected. Our phenotype–genotype correlation study confirmed that larger deletions are associated with more severe clinical course. The Bulgarian data support the thesis that the telomeric SMN gene could play a major role in determining SMA, while the NAIP or the centromeric SMN copy have a modifying effect on the phenotype. Hum Mutat 12:33–38, 1998. © 1998 Wiley-Liss, Inc. 相似文献
2.
Velasco E; Valero C; Valero A; Moreno F; Hernandez-Chico C 《Human molecular genetics》1996,5(2):257-263
Spinal muscular atrophy is an autosomal recessive disorder which affects
about 1 in 10,000 individuals. The three clinical forms of SMA were mapped
to the 5q13 region. Three candidate genes have been isolated and shown to
be deleted in SMA patients: the Survival Motor Neuron gene (SMN), the
Neuronal Apoptosis Inhibitory Protein gene (NAIP) and the XS2G3 cDNA. In
this report we present the molecular analysis of the SMN exons 7 and 8 and
NAIP exon 5 in 65 Spanish SMA families. NAIP was mostly deleted in type I
patients (67.9%) and SMN was deleted in 92.3% of patients with severe and
milder forms. Most patients who lacked the NAIP gene also lacked the SMN
gene, but we identified one type II patient deleted for NAIP exon 5 but not
for SMN exons 7 and 8. Two other patients carried deletions of NAIP exon 5
and SMN exon 7 but retained the SMN exon 8. Three polymorphic variants from
the SMN gene, showing changes on the sequence of the centromeric (cBCD541)
and telomeric copies of the SMN gene, were found. In addition, we show
several genetic rearrangements of the telomeric SMN gene, which include
duplication of this gene in one normal chromosome, and putative gene
conversion events in affected and normal chromosomes. Altogether these
results corroborate the high genetic variability of the SMA region.
Finally, we have determined the ratio between the number of centromeric and
telomeric copies of the SMN gene in parents of SMA patients, showing that
the majority of parents of types II and III patients carried three or more
copies of the cBCD541 gene; we suggest a relationship between the number of
copies of cBCD541 and the disease phenotype.
相似文献
3.
Hahnen Eric; Forkert Randolf; Marke Christine; Rudnik-Schoneborn Sabine; Schonling Jutta; Zerres Klaus; Creavin T.; Wirth Brunhilde 《Human molecular genetics》1995,4(10):1927-1933
Proximal spinal muscular atrophy (SMA) is a common autosomalrecessive neuromuscular disorder characterized by degenerationof anterior horn cells in the spinal cord leading to weaknessand wasting of voluntary muscles. Here we present the molecularanalysis of both SMA candidate genes, the survival motor neurongene (SMN; exons 7 and 8) and the neuronal apoptosis inhibitoryprotein gene (NAIP; exons 5, 6 and 13), in 195 patients and348 parents of SMA families mainly of German origin. The SMNgene is homozygously deleted for both exons 7 and 8 or exon7 only in 96% of type I SMA, 94% of type II SMA and 82% of typeIII SMA as well as in 0.3% of SMA parents. The NAIP gene ishomozygously deleted in 46% of type I SMA, 17% of type II SMA,7% of type III SMA and 2% of SMA parents. The frequencies ofdeletions in patients for both genes, SMN and NAIP, correspondto those for the NAIP gene only. SMA patients of this serieswho did not show deletions were clinically Indistinguishablefrom deleted patients. In addition to one unaffected motherof a type II SMA patient, we found homozygous deletions of theSMN gene exons 7 and 8 in six further unaffected individuais,all sibs of type II and III patients. These belonged to fourfamilies with affected and unaffected sibs who showed identicalhaplotypes for all SMA flanking markers; therefore, we had regardedthese families as chromosome 5 unlinked. All seven unaffectedindividuals in whom we detected SMA deletions do not show anysigns of muscle weakness and are physically inconspicuous. Thelargest divergence between age at onset of an affected subjectand the present age of unaffected deleted sibs is four decadesnow. The occurrence of SMN deletions in unaffected individualssuggests that other genes or mechanisms may be necessary toproduce the SMA phenotype. 相似文献
4.
P Burlet L Bürglen O Clermont S Lefebvre L Viollet A Munnich J Melki 《Journal of medical genetics》1996,33(4):281-283
Spinal muscular atrophy (SMA) is characterised by degeneration of anterior horn cells of the spinal cord and represents the second most common, lethal, autosomal recessive disorder after cystic fibrosis. Based on the criteria of the Internatinal SMA Consortium, childhood SMAs are classified into type I (Werdnig-Hoffmann disease), type II (intermediate form), and type III (Kugelberg-Welander disease). Recently, two genes have been found to be associated with SMA. The survival motor neurone gene (SMN) is an SMA determining gene as it is absent in 98.6% of patients. A second gene, XS2G3, or the highly homologous neuronal apoptosis inhibitory protein gene (NAIP) have been found to be more frequently deleted in type I than in the milder forms (types II and III). We investigated the correlation between the clinical phenotype and the genotype at this loci. A total of 106 patients were classified into type I (44), type II (31), and type III (31) and analysed using SMN, markers C212 and C272, and NAIP mapping upstream and downstream from SMN respectively. The combined analysis of all markers showed a large proportion of type I patients (43%) carried deletions of both SMN and its flanking markers (C212/272) and NAIP exon 5), as compared with none of the patients with type II or III SMA. The presence of large scale deletions involving these loci is specific to Werdnig-Hoffman disease (type I) and allows one to predict the severity of the disease in our series. 相似文献
5.
Different molecular basis for spinal muscular atrophy in South African black patients. 总被引:6,自引:0,他引:6
G Stevens T Yawitch J Rodda S Verhaart A Krause 《American journal of medical genetics》1999,86(5):420-426
Spinal muscular atrophy (SMA) is an autosomal recessive disorder occurring at a rate of between 1/5,000 and 1/10,000 births in most European countries. The phenotype results from the degeneration of the anterior horn cells of the spinal cord, resulting in symmetrical muscle weakness and wasting. The disorder can be classified according to the severity of the disease and the age of onset into three major types. Two candidate SMA genes, NAIP and SMN, isolated from the 5q13 region, have been reported to be homozygously deleted in approximately 30% and >95% of SMA patients, respectively. Black SMA patients have been reported to have facial muscle weakness more commonly. This study aimed to determine the molecular basis of SMA in South African black SMA patients. The SMN gene was found to be homozygously deleted in 65.5% (19/29) of patients, significantly less frequently than in previous studies. Similarly, the NAIP gene was homozygously deleted in a smaller number, 14% (4/29) of patients; 47% (9/19) of SMN deletion patients appeared to have deletions of telomeric exon 7, but not exon 8. In at least six of these patients a gene conversion event has occurred. No detectable deletions were found in 35% (10/29) of patients. Haplotype analysis in the nondeletion patients, using six closely linked markers, provided no evidence for a founder mutation. No mutations were found in exons 3 and intron 6 through exon 8 by sequence analysis of these nondeletion patients. It is proposed that the differences in the SMA phenotype observed in black patients may in part be explained by a different molecular basis. 相似文献
6.
Evidence for compound heterozygosity causing mild and severe forms of autosomal recessive spinal muscular atrophy. 总被引:1,自引:0,他引:1
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K Talbot N Rodrigues G Bernert R Bittner K Davies 《Journal of medical genetics》1996,33(12):1019-1021
Spinal muscular atrophy is an autosomal recessive disease of motor neurone degeneration which shows a variable phenotype. Two candidate genes show deletions in affected subjects but with no distinction between different forms of the disease. We report an unusual family in which mild and severe SMA coexists and patients are deleted for the SMN gene. The father is affected with late onset SMA; therefore this family shows pseudodominant inheritance. When typed using closely linked flanking markers the severely affected son does not share the same haplotype as his sib, who is deleted for SMN but shows no signs yet of SMA. This supports the hypothesis that differences in SMA phenotype can be explained by a multiple allele model. 相似文献
7.
G. Stevens T. Yawitch J. Rodda S. Verhaart A. Krause 《American journal of medical genetics. Part A》1999,86(5):420-426
Spinal muscular atrophy (SMA) is an autosomal recessive disorder occurring at a rate of between 1/5,000 and 1/10,000 births in most European countries. The phenotype results from the degeneration of the anterior horn cells of the spinal cord, resulting in symmetrical muscle weakness and wasting. The disorder can be classified according to the severity of the disease and the age of onset into three major types. Two candidate SMA genes, NAIP and SMN, isolated from the 5q13 region, have been reported to be homozygously deleted in ∼30% and >95% of SMA patients, respectively. Black SMA patients have been reported to have facial muscle weakness more commonly. This study aimed to determine the molecular basis of SMA in South African black SMA patients. The SMN gene was found to be homozygously deleted in 65.5% (19/29) of patients, significantly less frequently than in previous studies. Similarly, the NAIP gene was homozygously deleted in a smaller number, 14% (4/29) of patients; 47% (9/19) of SMN deletion patients appeared to have deletions of telomeric exon 7, but not exon 8. In at least six of these patients a gene conversion event has occurred. No detectable deletions were found in 35% (10/29) of patients. Haplotype analysis in the nondeletion patients, using six closely linked markers, provided no evidence for a founder mutation. No mutations were found in exons 3 and intron 6 through exon 8 by sequence analysis of these nondeletion patients. It is proposed that the differences in the SMA phenotype observed in black patients may in part be explained by a different molecular basis. Am. J. Med. Genet. 86:420–426, 1999. © 1999 Wiley-Liss, Inc. 相似文献
8.
Characterization of survival motor neuron (SMNT) gene deletions in asymptomatic carriers of spinal muscular atrophy 总被引:14,自引:1,他引:13
Wang CH; Xu J; Carter TA; Ross BM; Dominski MK; Bellcross CA; Penchaszadeh GK; Munsat TL; Gilliam TC 《Human molecular genetics》1996,5(3):359-365
Previous reports have established that the telomeric copy of the survival
motor neuron (SMNT) gene and the intact copy of the neuronal apoptosis
inhibitory protein (NAIP) gene are preferentially deleted in patients with
spinal muscular atrophy (SMA). Although deletions or mutations in the SMNT
gene are most highly correlated with SMA, it is not clear to what extent
NAIP or other genes influence the SMA phenotype, or whether a small
fraction of SMA patients actually have functional copies of both SMNT and
NAIP. To evaluate further the part of SMNT in the development of SMA, we
analyzed 280 asymptomatic SMA family members for the presence or absence of
SMNT exons 7 and 8. We report the following observations: (i) 4% of the
sample harbored a polymorphic variant of SMNT exon 7 that looks like a
homozygous deletion; (ii) approximately 1% of the parents are homozygously
deleted for both exons 7 and 8; (iii) one asymptomatic parent lacking both
copies of SMNT exons 7 and 8 displays a 'subclinical phenotype'
characterized by mild neurogenic pathology; (iv) another asymptomatic
parent lacking both SMNT exons showed no signs of motor neuron disorder by
clinical and neurodiagnostic analyses. The demonstration of polymorphic
variants of exon 7 that masquerade as homozygous nulls, and the
identification of SMA parents who harbor two disease alleles, serve as a
caution to those conducting prenatal tests with these markers.
相似文献
9.
Martin J. Somerville Alasdair G. W. Hunter Huguette L. Aubry Robert G. Korneluk Alex E. MacKenzie Linda C. Surh 《American journal of medical genetics. Part A》1997,69(2):159-165
The molecular genetic diagnosis of spinal muscular atrophy (SMA) has recently been complicated by the identification of two candidate genes, which are often deleted in affected individuals but are also occasionally deleted in apparently unaffected carriers. We present a compilation of genotypes, from our laboratory and recent reports, for the survival motor neuron (SMN) and neuronal apoptosis inhibitor protein (NAIP) genes. Bayesian analyses were used to generate probabilities for SMA when deletions are present or absent in SMN. We found that when the SMNT exon 7 is deleted, the probability of SMA can reach greater than 98% in some populations, and when SMNT is present, the probability of SMA is approximately 17 times less than the prior population risk. Deletion of NAIP exon 5, as well as SMNT exon 7, is associated with a 5-fold increased risk of type I SMA. Case studies are used to illustrate differing disease risks for pre- and postnatal testing, depending on the presence of information about clinical status or molecular results. These analyses demonstrate that deletion screening of candidate genes can be a powerful tool in the diagnosis of SMA. Am. J. Med. Genet. 69:159–165, 1997. © 1997 Wiley-Liss, Inc. 相似文献
10.
Frameshift mutation in the survival motor neuron gene in a severe case of SMA type I 总被引:9,自引:9,他引:9
Brahe C; Clermont O; Zappata S; Tiziano F; Melki J; Neri G 《Human molecular genetics》1996,5(12):1971-1976
Recently, a spinal muscular atrophy (SMA) determining gene, termed survival
motor neuron (SMN) gene, has been isolated from the 5q13 region and found
deleted in most patients. A highly homologous copy of this gene has also
been isolated and located in a centromeric position. We have analyzed 158
patients (SMA types I-IV) and found deletions of SMN exon 7 in 96.8%.
Mutations other than gross deletions seem to be extremely rare. In one of
the undeleted SMA type I patients, a newborn who survived for only 42 days,
we detected a maternally inherited 5 bp microdeletion in exon 3, resulting
in a premature stop codon. By RT-PCR and long range PCR amplification we
were able to show that the deletion belongs to the SMN gene, rather than to
the centromeric copy, and that the proposita had no paternal SMN gene.
Analysis of the neuronal apoptosis inhibitor protein (NAIP) gene, which
maps close to SMN and has been proposed as a SMA modifying gene, suggests
the presence of at least one full-length copy. Haplotype analysis of
closely linked polymorphic markers suggests that the proposita also lacks
the maternally derived copy of the centromeric homologue of SMN supporting
the hypothesis that the severity of the phenotype might depend on the
reduced number of centromeric genes in addition to the frameshift mutation.
相似文献
11.
Wirth B.; Hahnen E.; Morgan K.; DiDonato C.J.; Dadze A.; Rudnik-Schoneborn S.; Simard L.R.; Zerres K.; Burghes A.H.M. 《Human molecular genetics》1995,4(8):1273-1284
The candidate region for spinal muscular atrophy (SMA) has beendefined as a 750 kb interval on 5q13. In this study, we performedallelic association studies in 154 German SMA families withthe multicopy markers Ag1-CA (D5S1556); C212 (D5F149S1/S2) andcorrelated genotype data with deletion of candidate genes. Bothmulticopy markers recognize 03 alleles pro chromosome.Deletions were detected for all copies of the markers Ag1-CA(C272) and C212 in 13 of 88 (15%) type I SMA patients and threeof 48 (6%) type II patients. In all informative cases, the deletionwas inherited from one parent. In two further cases (one typeI and one type III SMA), de novo deletions of only one copyof Ag1-CA and C212 were found. In both cases the patients werehomozygously deleted for the survival motor neuron (SMN) gene(exons 7 and 8) but only the type I SMA patient was deletedfor the neuronal apoptosis inhibitory protein (NAIP) gene (exons5 and 6). A third case (type II SMA) showed de novo deletionof SMN, but not of Ag1-CA, C212 and NAIP. Specific alleles ofAg1-CA and C212 showed significant association with SMA, particularlyin type I SMA. When the number of marker copies defines genotypes,1,1 (one allele on each chromosome) is found to be increasedin type I SMA (50%) and 1, 2 (one allele on one chromosome andtwo alleles on the other one) in type II SMA (60%). The 2,2genotype (two alleles on each chromosome) was found in 4% oftype I and II patients. By comparison, pooled normal genotypefrequencies were 20, 44 and 36%, respectively. These resultssuggest a strong correlation between genotype and severity ofdisease. Based on these data we propose a model which indicatesthat type I SMA patients are composed of two severe alleles,type II of a mild and a severe, and type III of two mild alleles.Correlation of Ag1-CA genotype with deletion of the XS2G3/NAIPgenes indicates that most patients with a deletion have a 1,1genotype. Owing to the physical proximity of these markers,we propose that a large deletion occurs on type I SMA chromosomesthat removes DNA between C212 and XS2G3/NAIP and that type IISMA results from compound heterozygosity for mild (small deletion)and severe mutations. 相似文献
12.
Spinal muscular atrophies (SMA) are a group of motor neuron diseases characterized by degeneration of anterior horn cells
of the spinal cord and by muscular atrophy. Childhood-onset SMA is one of the most frequent autosomal recessive diseases and
a leading cause of infant mortality. The underlying biochemical defect of SMA is unknown. Recently two genes have been isolated
from the critical region at 5q13, the survival motor neuron (SMN) gene and the neuronal apoptosis inhibitor protein (NAIP) gene. Both genes are frequently deleted in SMA patients. NAIP is deleted in at least 45% of severely affected patients but less frequently in the milder forms. Homozygous deletions of
exon 7 of SMN are found in approximately 95% of patients independently of clinical severity. A few point mutations and microdeletions in
SMN have also been reported. This high frequency of deletions makes SMN analysis an important molecular diagnostic tool for childhood-onset SMA and greatly facilitates prenatal diagnosis. SMN analysis has also proven useful for the diagnosis of adult-onset SMA and variant forms. Although questions such as phenotype-genotype
correlation must still be solved, the isolation of SMN and adjacent genes constitutes an important step towards the understanding of the molecular basis of the disease.
Received: 5 February 1995 / Accepted: 13 June 1996 相似文献
13.
脊髓性肌萎缩患儿的NAIP基因分析 总被引:2,自引:0,他引:2
目的探讨脊髓性肌萎缩的基因型与临床表型(survivalmotorneurone,SMN)的关系。方法应用PCR技术对13例运动神经元型基因缺失的脊髓性肌萎缩患儿进一步进行神经原性细胞凋亡抑制蛋白(neuronalapoptosisinhibitoryproteinNAIP)基因分析(Ⅰ型5例,Ⅱ型4例,Ⅲ型4例)。结果2例Ⅰ型患儿携有NAIP基因缺失(2/5,40%)。结论NAIP基因缺失可能与脊髓性肌萎缩的临床表型严重程度有关 相似文献
14.
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16.
Schwartz M; Sorensen N; Hansen FJ; Hertz JM; Norby S; Tranebjaerg L; Skovby F 《Human molecular genetics》1997,6(1):99-104
In an analysis of 30 families affected by spinal muscular atrophy (SMA) we
have used the solid-phase minisequencing method to determine the ratio
between the number of telomeric and centromeric copies of the survival
motor neuron gene (SMN and cBCD541 respectively) on normal and SMA
chromosomes. This has enabled us to establish haplotypes with regard to SMN
and cBCD541, and estimate their frequencies, on both types of chromosomes.
Six predominant haplotypes were identified, three for normal chromosomes
and three for SMA chromosomes, characterized by having 0, 1, or 2 copies,
respectively, of cBCD541. We found evidence for the presence of patients
homozygous for a deletion of SMN and with only one copy of cBCD541, but
found none deleted for all copies of this gene. Several asymptomatic
carriers of SMA with only a single copy of SMN and no copy of cBCD541 were
identified. We could not confirm the hypothesis that the presence of more
copies of cBCD541 is correlated to a less severe course of the disease. The
frequencies of haplotypes characterized by having 0, 1, or 2 copies,
respectively, of cBCD541 were found to differ significantly between normal
and SMA chromosomes. This distribution can be explained by an
underrepresentation of the haplotype completely lacking SMN genes, which is
expected to cause early embryonic death in homozygotes. This first report
of a direct haplotype analysis of SMN and cBCD541 should help clarify the
role of cBCD541 in the pathogenesis of SMA.
相似文献
17.
Ogino S Gao S Leonard DG Paessler M Wilson RB 《European journal of human genetics : EJHG》2003,11(3):275-277
Most carriers of autosomal recessive spinal muscular atrophy (SMA) have only one copy of SMN1 because of SMN1 gene deletions or gene conversions from SMN1 to SMN2, which has only one base difference in coding sequence from SMN1. Using SMN gene dosage analysis, we determined the copy numbers of SMN1 and SMN2 in the general population as well as in SMA patients and carriers. Increased SMN1 copy number is associated with decreased SMN2 copy number in the general population; that is, SMN2 copy number was decreased to one or zero copies in 11 of 13 individuals with three or four copies of SMN1, whereas only 71 of 164 individuals with two copies of SMN1 had one or zero copies of SMN2 (P<0.01). SMN2 copy number was increased to three or four in a subset of SMN1 deletion/conversion carriers, and in most SMA patients with a milder phenotype. In conclusion, our data provide evidence that gene conversion from SMN2 to SMN1 occurs, and that SMN1 converted from SMN2 is present in the general population. 相似文献
18.
Unusual molecular findings in autosomal recessive spinal muscular atrophy. 总被引:6,自引:1,他引:6
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G Matthijs E Schollen E Legius K Devriendt N Goemans H Kayserili M Y Ap?k J J Cassiman 《Journal of medical genetics》1996,33(6):469-474
All three types of autosomal recessive spinal muscular atrophy map to chromosome 5q11.2-q13.3 and are associated with deletions or mutations of the SMN (survival motor neurone) gene. The availability of a test to distinguish between the SMN gene and its nearly identical centromeric copy cBCD541 allows molecular diagnosis. We have analysed patients from 24 Belgian and 34 Turkish families for the presence or absence of a deletion in the SMN gene. A homozygous deletion in the SMN gene was seen in 90% of unrelated SMA patients. A non-radioactive SSCP assay allows for a semiquantitative analysis of the copy number of the centromeric and SMN genes. Hence, direct carrier detection has become feasible under certain conditions. We observed a phenotypically normal male, father of an SMA type I patient, presenting with only a single copy of the SMN gene and lacking both copies of the cBCD541 gene. This illustrates that a reduction of the total number of SMN and cBCD541 genes to a single SMN copy is compatible with normal life. In another SMA type I family, there is evidence for a de novo deletion of the centromeric gene in a normal sib. This observation illustrates the susceptibility of the SMA locus to de novo deletions and rearrangements. 相似文献
19.
Smith M Calabro V Chong B Gardiner N Cowie S du Sart D 《European journal of human genetics : EJHG》2007,15(7):759-766
Spinal muscular atrophy (SMA) is one of the most common autosomal-recessive diseases, caused by absence of both copies of the survival motor neuron 1 (SMN1) gene. Identification of SMA carriers has important implications for individuals with a family history and the general population. SMA carriers are completely healthy and most are unaware of their carrier status until they have an affected child. A total of 422 individuals have been studied to identify SMA carriers. This cohort included 117 parents of children homozygously deleted for SMN1 (94% were carriers and 6% had two copies of SMN1; of these individuals, two in seven had the '2+0' genotype, two in seven were normal but had children carrying a de novo deletion and three in seven were unresolved), 158 individuals with a significant family history of SMA (47% had one copy, 49% had two copies and 4% had three copies of SMN1) and 146 individuals with no family history of SMA (90% had two copies, 2% had one copy and 8% had three copies of SMN1). The SMA carrier frequency in the Australian population appears to be 1/49 and the frequency of two-copy SMN1 alleles and de novo deletion mutations are both at least 1.7%. A multimodal approach involving quantitative analysis, linkage analysis and genetic risk assessment (GRA), facilitates the resolution of SMA carrier status in individuals with a family history as well as individuals of the general population, providing couples with better choices in their family planning. 相似文献
20.
Shin S Park SS Hwang YS Lee KW Chung SG Lee YJ Park MH 《Journal of Korean medical science》2000,15(1):93-98
Childhood-onset proximal spinal muscular atrophies (SMAs) are an autosomal recessive, clinically heterogeneous group of neuronopathies characterized by selective degeneration of anterior horn cells. The causative genes to be reported are survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) genes. The deletion of telomeric copy of SMN (SMN(T)) gene was observed in over 95% of SMAs. The deletion rate of NAIP gene is 20-50% according to disease severity. The objective of this article is to genetically characterize the childhood-onset spinal muscular atrophy in Koreans. Five Korean families (14 constituents containing 5 probands) with SMA were included in this study. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used for the deletion analysis of SMN(T). Multiplex PCR method was used for NAIP analysis. Four probands showed deletion of SMNT gene. Deletion of SMN(C) (centromeric SMN) gene was found in one proband who did not show the deletion of SMN(T) gene and in the father of one proband who showed the deletion of SMN(T) gene. The deletion of NAIP gene was not found among all the studied individuals. The extent of deletion in Koreans was smaller than that in other studied population. PCR-RFLP deletion analysis can be applied to diagnose SMA and make a prenatal diagnosis. 相似文献