Abstract
Abstract Background Collagen VI-related disorders are a group of muscular diseases characterized by muscle wasting and weakness, joint contractures, distal laxity, serious respiratory dysfunction and cutaneous alterations, due to mutations in the COL6A1, COL6A2 and COL6A3 genes, encoding for collagen VI, a critical component of the extracellular matrix. The severe Ullrich congenital muscular dystrophy (UCMD) can be due to autosomal recessive mutations in one of the three genes with a related 25% recurrence risk. In the majority of UCMD cases nevertheless, the underlying mutation is thought to arise de novo and the recurrence risk is considered as low. Methods and results Here we report a family with recurrence of UCMD in two half-sibs. In both, the molecular analysis revealed heterozygosity for the c.896G > A missense mutation in COL6A1 exon 10 (Gly299Glu) and for the COL6A1 c.1823-8G > A variation within COL6A1 intron 29. The intronic variation was inherited from the father and RNA analysis in skin fibroblasts allowed to exclude its role in affecting COL6A1 transcript processing. The Gly299Glu mutation occurred apparently de novo in the two sibs. Conclusion The described mutational segregation strongly suggests the occurrence of paternal germline mosaicism. This is the first report of UCMD recurrence due to a germline mosaic COL6 gene mutation. Mosaicism deserves to be considered as possible inheritance pattern in genetic counseling and recurrence risk estimation in collagen VI-related diseases.
| Original language | English |
|---|---|
| Article number | 1900 |
| Pages (from-to) | 533-536 |
| Number of pages | 4 |
| Journal | European Journal of Paediatric Neurology |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sep 1 2015 |
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Keywords
- Collagen VI
- Germline mosaicism
- UCMD
ASJC Scopus subject areas
- Clinical Neurology
- Pediatrics, Perinatology, and Child Health
- Medicine(all)
Cite this
Paternal germline mosaicism in collagen VI related myopathies. / Armaroli, Annarita; Trabanelli, Cecilia; Scotton, Chiara; Venturoli, Anna; Selvatici, Rita; Brisca, Giacomo; Merlini, Luciano; Bruno, Claudio; Ferlini, Alessandra; Gualandi, Francesca.
In: European Journal of Paediatric Neurology, Vol. 19, No. 5, 1900, 01.09.2015, p. 533-536.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Paternal germline mosaicism in collagen VI related myopathies
AU - Armaroli, Annarita
AU - Trabanelli, Cecilia
AU - Scotton, Chiara
AU - Venturoli, Anna
AU - Selvatici, Rita
AU - Brisca, Giacomo
AU - Merlini, Luciano
AU - Bruno, Claudio
AU - Ferlini, Alessandra
AU - Gualandi, Francesca
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Abstract Background Collagen VI-related disorders are a group of muscular diseases characterized by muscle wasting and weakness, joint contractures, distal laxity, serious respiratory dysfunction and cutaneous alterations, due to mutations in the COL6A1, COL6A2 and COL6A3 genes, encoding for collagen VI, a critical component of the extracellular matrix. The severe Ullrich congenital muscular dystrophy (UCMD) can be due to autosomal recessive mutations in one of the three genes with a related 25% recurrence risk. In the majority of UCMD cases nevertheless, the underlying mutation is thought to arise de novo and the recurrence risk is considered as low. Methods and results Here we report a family with recurrence of UCMD in two half-sibs. In both, the molecular analysis revealed heterozygosity for the c.896G > A missense mutation in COL6A1 exon 10 (Gly299Glu) and for the COL6A1 c.1823-8G > A variation within COL6A1 intron 29. The intronic variation was inherited from the father and RNA analysis in skin fibroblasts allowed to exclude its role in affecting COL6A1 transcript processing. The Gly299Glu mutation occurred apparently de novo in the two sibs. Conclusion The described mutational segregation strongly suggests the occurrence of paternal germline mosaicism. This is the first report of UCMD recurrence due to a germline mosaic COL6 gene mutation. Mosaicism deserves to be considered as possible inheritance pattern in genetic counseling and recurrence risk estimation in collagen VI-related diseases.
AB - Abstract Background Collagen VI-related disorders are a group of muscular diseases characterized by muscle wasting and weakness, joint contractures, distal laxity, serious respiratory dysfunction and cutaneous alterations, due to mutations in the COL6A1, COL6A2 and COL6A3 genes, encoding for collagen VI, a critical component of the extracellular matrix. The severe Ullrich congenital muscular dystrophy (UCMD) can be due to autosomal recessive mutations in one of the three genes with a related 25% recurrence risk. In the majority of UCMD cases nevertheless, the underlying mutation is thought to arise de novo and the recurrence risk is considered as low. Methods and results Here we report a family with recurrence of UCMD in two half-sibs. In both, the molecular analysis revealed heterozygosity for the c.896G > A missense mutation in COL6A1 exon 10 (Gly299Glu) and for the COL6A1 c.1823-8G > A variation within COL6A1 intron 29. The intronic variation was inherited from the father and RNA analysis in skin fibroblasts allowed to exclude its role in affecting COL6A1 transcript processing. The Gly299Glu mutation occurred apparently de novo in the two sibs. Conclusion The described mutational segregation strongly suggests the occurrence of paternal germline mosaicism. This is the first report of UCMD recurrence due to a germline mosaic COL6 gene mutation. Mosaicism deserves to be considered as possible inheritance pattern in genetic counseling and recurrence risk estimation in collagen VI-related diseases.
KW - Collagen VI
KW - Germline mosaicism
KW - UCMD
UR - http://www.scopus.com/inward/record.url?scp=84938740452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938740452&partnerID=8YFLogxK
U2 - 10.1016/j.ejpn.2015.04.002
DO - 10.1016/j.ejpn.2015.04.002
M3 - Article
C2 - 25978941
AN - SCOPUS:84938740452
VL - 19
SP - 533
EP - 536
JO - European Journal of Paediatric Neurology
JF - European Journal of Paediatric Neurology
SN - 1090-3798
IS - 5
M1 - 1900
ER -