Table 1.

Clinical features and collagen VI molecular and biochemical status.

Patient	BM1	BM2	BM3	BM4	BM5	UCMD6	UCMD7
Current age (years)	47	39	†	42	7	16	21
Presentation	Birth: hip dislocation	2 years	Birth: hip dislocation	Infancy	Infancy: hypotonia and torticollis	Infancy: muscle weakness and progressive joint contractures	Birth: hip dislocation
Contractures	Elbows: + Knee: ++	Elbows: +++	Elbows: +++	Elbows:+++ Long finger flexors: +++ Achilles tendons: +++	None	Elbows: +++ Hips: +++ Knees: +++ Achilles tendons: +++	Elbows:+++ Hips:+++ Knees:+++
Maximum motor ability	Independent ambulation	Independent ambulation	Independent ambulation	Independent ambulation. Using walking frame since age 40 years	Independent ambulation	Independent ambulation. Wheelchair dependence since age 3.5 years	Independent ambulation. Wheelchair dependence since age 10 years
Respiratory function: % predicted forced vital capacity (FVC)	Not available	Not available	FVC 70% (age 23 years)	Not available	FVC 80% (age 6 years)	FVC 15% (age 9 years)	FVC 40% (age 12 years)
Mutation	COL6A1: intron 3 G > A + 1, causing the activation of a cryptic donor splice site in exon 3, resulting in an in-frame 66 nucleotide deletion	Heterozygous Gly341Val in exon 14 of COL6A1	Heterozygous mutation resulting in skipping of exon 14 of COL6A1	Heterozygous c.877G > A; p.Gly293Arg in exon 10 of COL6A1	Heterozygous c.877G > A; p.Gly293Arg in exon 10 of COL6A1	Heterozygous c.6210 + 1G > A in intron 16 of COL6A3	Homozygous c.1776 + 1G > A in intron 27 of COL6A1
Muscle collagen VI double immuno-labelling	Muscle not available	Muscle not available	Reduced at the sarcolemma	Muscle not available	Muscle not available	Reduced at the sarcolemma	Muscle not available
Fibroblast collagen VI immuno-labelling	Moderate reduction in the ECM; increased intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗	Moderate reduction in the ECM; increased intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗	Moderate reduction in the ECM; increased intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗	Moderate reduction in the ECM; increased intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗	Marked reduction in the ECM; marked intracellular accumulation following permeabilisation. Overall collagen VI reduction:∗∗∗	Marked reduction in the ECM; marked intracellular accumulation following permeabilisation. Overall collagen VI reduction:∗∗∗	Marked reduction in the ECM; marked intracellular accumulation following permeabilisation. Overall collagen VI reduction:∗∗∗
Flow cytometry result•	41.2%	45.6%	28.1%	44.6%	50.5%	70.7%	60.0%
References	[26,27]					[1,8,9]	[1,8]

Patient	UCMD8	UCMD9	UCMD10	UCMD11	UCMD12	UCMD13
Current age (years)	19	15	30	8	23	9
Presentation	1.5 years	Birth: hip dislocation and hypotonia	1 year	1 year	Birth: talipes	Birth: talipes
Contractures	Elbows: ++ Long finger flexors: + Knees: + Achilles tendons: +++	Elbows: ++ Hips: +++ Knees: +++	Elbows:+++ Hips: ++ Knees: + Achilles tendons: +++	Elbows: ++ Knees: +	Elbows: ++ Achilles tendons: ++	Elbows: ++ Hips: + Knees: ++ Achilles tendons: ++
Maximum motor ability	Independent ambulation. Wheelchair dependence since age 11 years	Independent ambulation. Wheelchair dependence since 6 years of age	Independent ambulation. Wheelchair dependence since age 15 years	Independent ambulation. Wheelchair dependence since age 8 years	Independent ambulation. Part-time wheelchair use since age 18 years	Independent ambulation. Wheelchair dependence since age 8 years
Respiratory function: % predicted forced vital capacity (FVC)	FVC 8% (age 15 years)	FVC 16% (age 12 years)	FVC 17% (age 19 years)	Not performed	FVC 38% (age 18 years)	FVC 56% (age 7 years)
Mutation	Homozygous Cys777Arg in exon 26 of COL6A2	Heterozygous donor splice site change in intron 16 of COL6A3	Homozygous c.2839_2850del; p.Leu947_Gly950del in exon 28 of COL6A2	Homozygous mutation r.2839_2850del; p.Leu947Gly950del detected in exon 28 of the COL6A2 gene	Heterozygous mutation r.868G>A; p.Gly290Arg detected in exon 10 of the COL6A1 gene	Heterozygous mutation r.868G>C; p.Gly290Arg detected in exon 10 of the COL6A1 gene
Muscle collagen VI double immuno-labelling	Muscle not available	Muscle not available	Reduced at the sarcolemma	Reduced at the sarcolemma	Muscle not available	Reduced at the sarcolemma
Fibroblast collagen VI immuno-labelling	Marked reduction in the ECM; marked intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗∗	Marked reduction in the ECM; marked intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗∗	Marked reduction in the ECM; marked intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗∗	Marked reduction in the ECM; marked intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗∗	Marked reduction in the ECM; marked intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗∗	Marked reduction in the ECM; marked intracellular accumulation following permeabilisation. Overall collagen VI reduction: ∗∗∗
Flow cytometry result•	68.6%	65.9%	85.8%	72.5%	74.9%	68.8%
References	[1,8]	[1,8,9]	[1,20]		[1,20]

Flow cytometry results for controls (difference between permeabilised cells and non-permeabilised cells): 19.6–42.9%.

ECM = extracellular matrix.

+ = mild contractures (5°–10°).

++ = moderate contractures (>10° but <30°).

+++ = severe contractures (>30°).

∗ = mild collagen VI reduction in ECM.

∗∗ = moderate collagen VI reduction in ECM.

∗∗∗ = marked collagen VI reduction in ECM.

^†Deceased (died of lung cancer at age 30 years).

^•Difference between permeabilised cells and non-permeabilised cells (= intracellular accumulation).