脊髓性肌萎缩症SMN1基因 2+0基因型携带者的家系研究

doi:10.16288/j.yczz.20-319

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Hereditas(Beijing) ›› 2021, Vol. 43 ›› Issue (2): 160-168.doi: 10.16288/j.yczz.20-319

• Research Article • Previous Articles Next Articles

Familial study of spinal muscular atrophy carriers with SMN1 (2+0) genotype

Yanyan Cao¹(), Miaomiao Cheng¹, Fang Song¹(), Yujin Qu¹, Jinli Bai¹, Hong Wang¹

¹ Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China

Received:2020-10-17 Online:2021-02-16 Published:2020-12-24
Supported by:
the National Key Research and Development Program of China(2016YFC0901505);CAMS Initiative for Innovative Medicine(2016-I2M-1-008);the China Postdoctoral Science Foundation(2018M630108);National Natural Science Foundation of China(81500979);Beijing Natural Science Foundation(5163028)

Abstract

Abstract:

Spinal muscular atrophy (SMA) is a common childhood neuromuscular disease inherited in an autosomal recessive pattern. The majority of SMA patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene. As a special SMA carrier, the (2+0) genotype ofSMN1 poses a great challenge for carrier screening and family genetic counseling. A previous study showed that polymorphisms of g.27134 T>G and g.27706_27707delAT had a predictive effect on (2+0) carriers in the Ashkenazi Jewish population. To further explore whether these two polymorphisms are specific to the Chinese population, the present study recruited 44 family members and 204 controls with knownSMN1copy number. These 44 family members were from nine unrelated SMA families withSMN1 homozygous deletion, and one of the proband parents was suspected to be a (2+0) carrier. Multiplex ligation-dependent probe amplification (MLPA) and short tandem repeat (STR) linkage analyses were used to determine the (2+0) genotype and polymorphism screening. Finally, by analyzing theSMN copies and haplotype from three generations of family members and two generations of multi-child families, ten individuals in nine families were confirmed as (2+0) carriers. Moreover, only one individual with three copies ofSMN1 carried the two polymorphisms of g.27134 T>G and g.27706_27707delAT. Therefore, we provided precise genetic counseling for these SMA families after confirming the (2+0) carriers. The association between the polymorphisms of g.27134T>G and g.27706_27707delAT and Chinese (2+0) carriers might be weak. Hence, it is necessary to find specific polymorphisms in the Chinese population to improve the detection rate of (2+0) carriers.

Key words: spinal muscular atrophy, SMN1, (2+0) genotype, STR linkage analysis, polymorphism

Yanyan Cao, Miaomiao Cheng, Fang Song, Yujin Qu, Jinli Bai, Hong Wang. Familial study of spinal muscular atrophy carriers with SMN1 (2+0) genotype[J]. Hereditas(Beijing), 2021, 43(2): 160-168.

Figures/Tables 6

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References 12

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SMN1拷贝数	SMN1基因型	先证者(%)	先证者父亲(%)	先证者母亲(%)	先证者祖父/母(%)	先证者外祖父/母(%)	先证者同胞(%)
0	0+0	9 (100)	0	0	0	0	0
1	1+0	0	6 (66.7)	3 (33.3)	3 (50)	4 (44.4)	0
2	2+0	0	3(33.3)	6 (66.7)	0	0	1 (50)
3	2+1	0	0	0	3 (50)	5 (55.6) ^a	1 (50)
合计	-	9	9	9	6	9	2

家系	I (祖父/祖母或外祖父/外祖母)	II (父亲/母亲)	III (先证者/同胞)
#1	1/3	2/1	0
#2	3/1	1/2	0
#3	1/3	1/2	0
#4	3/1	2/1	0
#5	1/3	1/2	0
#6	1/3	1/2	0
#7	1/3	2/1	0
#8	3/NA	1/2	0/2
#9	NA	1/2	0/3
合计	8	9	9

多态位点	SMA家系成员(SMN1基因型)				对照组(SMN1拷贝数)
多态位点	0+0	1+0	2+0	2+1	2拷贝 ^a	3拷贝	4拷贝
g.27134T>G	0	0	0	0	0	1 (6.3%)	0
g.27706_27707delAT	0	0	0	0	0	1 (6.3%)	0
筛查例数	9	16	10	9	187	16	1

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Familial study of spinal muscular atrophy carriers with SMN1 (2+0) genotype

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