Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan.
OBJECTIVE
To determine the frequency of primary collagen VI deficiency in congenital muscular dystrophy (CMD) in Japan and to establish the genotype-phenotype correlation.


METHODS
We performed immunohistochemistry for collagen VI in muscles from 362 Japanese patients with CMD, and directly sequenced the three collagen VI genes, COL6A1, COL6A2, and COL6A3, in patients found to have collagen VI deficiency.


RESULTS
In Japan, primary collagen VI deficiency accounts for 7.2% of congenital muscular deficiency. Among these patients, five had complete deficiency (CD) and 29 had sarcolemma-specific collagen VI deficiency (SSCD). We found two homozygous and three compound heterozygous mutations in COL6A2 and COL6A3 in all five patients with CD, and identified heterozygous missense mutations or in-frame small deletions in 21 patients with SSCD in the triple helical domain (THD) of COL6A1, COL6A2, and COL6A3. All mutations in SSCD were sporadic dominant. No genotype-phenotype correlation was seen.


CONCLUSIONS
Primary collagen VI deficiency is the second most common CMD after Fukuyama type CMD in Japan. Dominant mutations located in the N-terminal side from the cysteine residue in the THD of COL6A1, COL6A2, and COL6A3 are closely associated with SSCD.
Okada
M
M
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Ogawahigashi-cho, Kodaira, Tokyo, Japan.
Kawahara
G
G
Noguchi
S
S
Sugie
K
K
Murayama
K
K
Nonaka
I
I
Hayashi
Y K
YK
Nishino
I
I
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D009154:Mutation