The clinical, myopathological, and molecular characteristics of 26 Chinese patients with dysferlinopathy: a high proportion of misdiagnosis and novel variants

Wang, Ning; Han, Xu; Hao, Shengpu; Han, Jingzhe; Zhou, Xiaomeng; Sun, Shuyan; Tang, Jin; Lu, Yanpeng; Wu, Hongran; Ma, Shaojuan; Song, Xueqin; Ji, Guang

doi:10.1186/s12883-022-02905-w

Table 1 Clinical data and pathogenic variants obtained in the cohort

From: The clinical, myopathological, and molecular characteristics of 26 Chinese patients with dysferlinopathy: a high proportion of misdiagnosis and novel variants

Patient No	Sex	Age at onset	disease duration	CK fold	Pheno-type	Misdiagnose	Dysferlin on IHC	Zygos-ity	Mutation type	Genomic position	Nucleotide changes	Protein change	ACMG/AMP codes	ACMG classification
1	M	26	2	35.3	LGMDR2	polymyositis	-	Het	Canonical-splice	chr2:71708069	c.144 + 1G > A	splicing	PVS1 + PM2 + PP4_ moderate	Pathogenic
1	M	26	2	35.3	LGMDR2	polymyositis	-	Het	splice	chr2:71753481	c.1273 + 5G > C	splicing	PVS1 + PM2 + PP4_ moderate	Pathogenic
2	M	18	0.1	11.6	HyperCK	viral myocarditis	-	Hom	missense	chr2:71747946*1	c.965T > C	p. L322P	PS1 + PM2 + PM3 + PP4_ moderate	Pathogenic
3	M	16	0.5	6	HyperCK	viral myocarditis	strongly reduced	Het	missense	chr2:71797459	c.3026 A > G*	p. E1009G	PM2 + PP4	VUS
3	M	16	0.5	6	HyperCK	viral myocarditis	strongly reduced	Het	nonsense	chr:71,797,809	c.3112 C > T	p. R1038X	PVS1 + PS1 + PM2 + PP4_moderate	Pathogenic
4	M	25	0.1	61.3	HyperCK	dermatomyositis	-	Het	nonsense	chr2:71797809	c.3112 C > T	p. R1038X	PVS1 + PS1 + PM2 + PP4_ moderate	Pathogenic
4	M	25	0.1	61.3	HyperCK	dermatomyositis	-	Het	nonsense	chr2:71838459	c.3988 C > T	p. Q1330X	PVS1 + PS1 + PM2 + PP4_ moderate	Pathogenic
5	M	29	0	15.4	HyperCK	viral myocarditis	-	Het	missense	chr2:71801439	c.3286 C > A*	p. R1096S	PM2 + PP4	VUS
5	M	29	0	15.4	HyperCK	viral myocarditis	-	Het	nonsense	chr2:71906245	c.5826 C > A*	p. C1942X	PVS1 + PM2 + PM3 + PP4_ moderate	Pathogenic
6	F	24	7	18.3	LGMDR2		-	Het	canonical-splice	chr2:71747339	c.937 + 1G > A	splicing	PVS1 + PS1 + PM2 + PP4_ moderate	Pathogenic
6	F	24	7	18.3	LGMDR2		-	Het	missense	chr2:71797407	c.2974T > C	p. Trp992Arg	PS1 + PM2 + PP4_ moderate	likely Pathogenic
7	M	25	10	6.9	LGMDR2	polymyositis	strongly reduced	Hom	missense	chr2:71753461	c.1165G > A	p. Glu389Lys	PM2 + PM3_Supporting + PP4	VUS
8	M	16	6	19.4	LGMDR2		-	Het	nonsense	chr2:71886125	c.4756 C > T	p. R1586X	PVS1 + PS1 + PM2 + PM3 + PP4_ supporting	Pathogenic
8	M	16	6	19.4	LGMDR2		-	Het	frameshift	chr2:7189462071894620;	c.5316dupC*	p. S1772fs	PVS1 + PM2 + PM3 + PP4_ moderate	Pathogenic
9	F	16	10	20.6	LGMDR2		-	Het	nonsense	chr2:71740998	c.610 C > T	p. Arg204Term	PVS1 + PS1 + PM2 + PP4_ moderate	Pathogenic
9	F	16	10	20.6	LGMDR2		-	Het	duplication	23–30 Exon	exon22-29 suspected duplication variant*		PM2 + PP4	VUS
10	M	27	4	30.3	LGMDR2		-	Het	missense	chr2-71791250	c.2418 C > A*	p. Y806X	PVS1 + PM2 + PM3_strong + PP4_ moderate	Pathogenic
10	M	27	4	30.3	LGMDR2		-	Het	missense	chr2:71896337	c.5525G > A	p. G1842D	PS1 + PM2 + PM3_strong + PP4_ moderate	Pathogenic
11	F	21	1	26.7	LGMDR2	polymyositis	strongly reduced	Hom	missense	chr2:71894601	c.5296G > A	p. Glu1766Lys	PS1 + PM2 + PM3_supporting + PP4_supporting	Pathogenic
12	M	18	4	49.6	LGMDR2	polymyositis	-	Het	canonical-splice	chr2:71747339	c.937 + 1G > A	splicing	PVS1 + PM2 + PP4_ moderate	Pathogenic
12	M	18	4	49.6	LGMDR2	polymyositis	-	Het	missense	chr2:71896321	c.5509G > A	p. D1837N	PS1 + PM2 + PP4_ moderate	likely Pathogenic
13	F	18	1	36.3	LGMDR2	polymyositis	strongly reduced	Het	missense	chr2:71827854	c.3725G > A	p. R1242H	PS1 + PP4_ supporting	VUS
13	F	18	1	36.3	LGMDR2	polymyositis	strongly reduced	Het	missense	chr2:71886111	c.4742G > A	p. R1581H	PS1 + PM2 + PP4_ supporting	likely Pathogenic
14	F	33	2	32	LGMDR2	polymyositis	-	Het	missense	chr2:71892431	c5197A > G	p. I1733V	PS1 + PM2 + PP4_ moderate	likely Pathogenic
14	F	33	2	32	LGMDR2	polymyositis	-	Het	missense	chr2:71894563	c.5258 A > G*	p.H1753R	PM2 + PP4	VUS
15	F	35	1	15	LGMDR2	polymyositis	-	Het	nonsense	Chr2:71742762	c.673 C > T*	p. Q225X	PVS1 + PM2 + PP4_ moderate	Pathogenic
15	F	35	1	15	LGMDR2	polymyositis	-	Het	missense	Chr2:71906214	c.5795T > A*	p.M1932K	PM2 + PP4	VUS
16	F	27	3	26.7	LGMDR2		strongly reduced	Het	nonsense	chr2:71709020	c.156G > A*	p. W52X	PVS1 + PS2 + PM3 + PP4_ moderate	Pathogenic
16	F	27	3	26.7	LGMDR2		strongly reduced	Het	missense	chr2:71896779	c.5570 A > G	p.H1857R	PS1 + PM2 + PM3 + PP4_moderate	Pathogenic
17	M	35	8	19.1	LGMDR2	polymyositis	-	Het	frameshift	chr2:71762413	c.1375dupA	p. Met459Asnfs*15	PVS1 + PM2 + PP4_ moderate	Pathogenic
17	M	35	8	19.1	LGMDR2	polymyositis	-	Het	frameshift	chr2:71825821	c.3648delA*	splicing	PVS1 + PM2 + PP4_ moderate	Pathogenic
18	F	31	17	4.3	LGMDR2	polymyositis	-	Het	missense	chr2:71742844	c.755 C > T	p. T252M	PS1 + PM2 + PP4_ moderate	Likely pathogenic
18	F	31	17	4.3	LGMDR2	polymyositis	-	Het	duplication		Exon41-52suspected duplication variant*		PM4 + PP4	VUS
19	F	26	10	7.6	LGMDR2		-	Het	frameshift	chr2:71743324–71,743,328	c.808_811del*	p. F271Tfs*16	PVS1 + PM2 + PP4_ moderate	Pathogenic
19	F	26	10	7.6	LGMDR2		-	Het	nonsense	chr2:71797809	c.3112 C > T	p. R1038X	PVS1 + PS1 + PM2 + PP4_ moderate	Pathogenic
20	M	37	15	16.1	LGMDR2	polymyositis	-	Het	frameshift	chr2:71801368–71,801,370	c.3216_3217delCT	p. L1074Ffs*39	PVS1 + PM2 + PP4_ moderate	Pathogenic
20	M	37	15	16.1	LGMDR2	polymyositis	-	Het	missense	chr2:71891543	c.5032T > C	p.C1678R	PM2 + PP4	Likely pathogenic
21	M	18	6	34.5	LGMDR2	polymyositis	-	Hom	frameshift	chr2:71891489–71,891,509	c.4979_4998delGTGAGACGGTCGTCGACCTGinsA*	p. G1660Efs	PVS1 + PM2 + PM3_supporting + PP4_moder-ate	Pathogenic
22	M	29	4	35.8	MM	polymyositis	-	Het	canonical-splice	chr2:71795213	c.2643 + 1G > A	splicing	PVS1 + PS1 + PM2 + PP4_ moderate	Pathogenic
22	M	29	4	35.8	MM	polymyositis	-	Het	missense	chr2:71816726	c.3352G > A*	p. G1118S	PM2 + PP4	VUS
23	F	21	5	29.6	MM	polymyositis	strongly reduced	Het	missense	chr2:71797407	c.2974T > C	p. W992R	PS1 + PM2 + PP4_ supporting	Pathogenic
23	F	21	5	29.6	MM	polymyositis	strongly reduced	Het	frameshift	chr2:71896814–71,896,814	c.5606dupG	p. R1870Efs*12	PVS1 + PS1 + PM2 + PP4_ supporting	Pathogenic
24	M	17	1	59.3	MM		-	Het	nonsense	chr2:71740998	c.610 C > T	p. Arg204Term	PVS1 + PS1 + PM2 + PM3 + PP4_ moderate	Pathogenic
24	M	17	1	59.3	MM		-	Het	nonsense	chr2:71839831	c.4228 C > T	p. Q1410X	PVS1 + PM2 + PM3 + PP4_ moderate	Pathogenic
25	F	20	7	8.4	MM		-	Het	nonsense	chr2:71797809	c.3112 C > T	p. R1038X	PVS1 + PM3 + PM2 + PP4_ moderate	Pathogenic
25	F	20	7	8.4	MM		-	Het	nonsense	chr2:71766369	c.1480G > T	p. E494X	PVS1 + PM3 + PP4_moderate + BP4	Pathogenic
26	F	28	3	11.6	LGMDR2	polymyositis	-	Het	canonical-splice	chr2:71747339	c.937 + 1G > A	splicing	PVS1 + PS1 + PM2 + PP4_ moderate	Pathogenic

*, novel variant; -, completely reduction; Het, heterozygous; Hom, homozygous; LGMD R2, limb-girdle muscular dystrophy type R2; MM, Miyoshi Myopathy; HyperCK, asymptomatic hyperCKemia; VUS, the clinical significance is unclear; transcript number (NM_), NM_003494.4

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