Clinical and genetic interpretation of uncertain DMD missense variants: evidence from mRNA and protein studies

Table 1 Clinical and pathological features of the nine enrolled patients

Patient number	Phenotype	Age, years/sex	Age at onset, years	Symptom(s) at onset	Calf hypertrophy	Tendon contractures	Muscle pain	Age at appearance of Gowers' sign, years	Age at waddling gait, years
P1	DMD	4.3	3.8	HyperCKemia; fatigue	+	–	–	4.3	–
P2	DMD	8.8	3	Delayed motor milestones	+	+	–	3	8
P3	DMD	7	3.5	Difficulties in running and jumping	+	+	–	4	6.5
P4	BMD	4.1	3	Difficulties in running	+	–	–	–	–
P5	BMD	17.2	12	Progressive lower limb weakness	+	–	–	12	–
P6	BMD	3.9	3.3	HyperCKemia	+	–	–	–	–
P7	BMD	4.7	2	Myalgia	–	–	+	–	–
P8	BMD	7.5	5.7	HyperCKemia	–	–	–	–	–
P9	BMD	3.6	3	Myalgia	–	–	+	–	–

Patient number	Age at loss of ambulation, years	Distribution of weakness	CK (IU/L)	Pathological pattern	Dystrophin-N	Dystrophin-C	Dystrophin-R	α-sarcoglycan	β-sarcoglycan	γ-sarcoglycan
P1	–	Proximal	7621	Dystrophic	+ /–	+ /–	+ ~ + +	+ + +	+ + ~ + + +	+ + +
P2	–	Proximal	13,272	Dystrophic	–	–	– ~ + /–	+ + +	+ + ~ + + +	+ + ~ + + +
P3	–	Generalized	25,440	Dystrophic	–	–	–	+ /–	+ /–	+ + +
P4	–	None	1544	Dystrophic	+ +	+ +	+ +	+ + +	+ +	+ + ~ + + +
P5	–	Proximal	7655	Dystrophic	– ~ + /–	+ +	+ + +	+ + +	+ + +	+ + +
P6	–	None	6223	Dystrophic	+ /–	+	+ +	+ + ~ + + +	+ /– ~ +	+ + +
P7	–	None	1474	Myopathic changes	+ +	+ + +	+ + +	+ + +	+ +	+ + +
P8	–	None	3832	Myopathic changes	+ +	+ +	+ +	+ + ~ + + +	+ + ~ + + +	+ + ~ + + +
P9	–	None	1807	Mild myopathic changes	+ +	+ +	+ + +	+ + +	+ +	+ + +

Protein expression based on immunohistochemical staining sections was graded into absence with or without isolated revertant fibers –, severe reduction + /–, partial reduction + , slight reduction + + , and positive expression + + + . Phenotype of a patient with dystrophinopathy was determined as BMD or DMD according to the following criteria [4]: BMD, presenting with no obvious muscle weakness by 5 years of age and a slight to partial reduction in the expression of dystrophin-C regardless of the expression of dystrophin-R and dystrophin-N; DMD, proximal muscle weakness evident by 5 years of age and complete or almost complete deficiency of dystrophin, especially the dystrophin-C. DMD, Duchenne muscular dystrophy; BMD, Becker muscular dystrophy; CK, creatine kinase

ISSN: 1750-1172