Abstract | BACKGROUND: METHODS: We analyzed POMT2 in six CMD patients, who had severe diffuse muscle weakness, generalized joint contractures, microcephaly, severe mental retardation and elevated CK levels. Eye involvement was absent or limited to myopia or strabismus. We sequenced the coding regions of POMT2 using genomic DNA and cDNA generated from blood lymphocytes or B lymphoblastoid cell lines. Quantitative PCR analysis of genomic DNA was used to identify and determine the breakpoints of large deletions. RESULTS: We report five novel mutations in POMT2, four of which were outside of coding exons, two large genomic deletions and two intronic single base substitutions that induced aberrant mRNA splicing. CONCLUSIONS: Large scale DNA rearrangements (such as large deletions) and cryptic splice mutations, that can be missed on standard sequencing of genomic DNA, may be relatively common in POMT2. Additional techniques, such as sequencing of cDNA are needed to identify all mutations. These results also confirm that POMT2 mutations are an important cause of the less severe alpha-dystroglycanopathy phenotypes.
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Authors | Akiko Yanagisawa, Céline Bouchet, Susana Quijano-Roy, Sandrine Vuillaumier-Barrot, Nigel Clarke, Sylvie Odent, Diana Rodriguez, Norma B Romero, Makiko Osawa, Tamao Endo, Ana Lia Taratuto, Nathalie Seta, Pascale Guicheney |
Journal | European journal of medical genetics
(Eur J Med Genet)
2009 Jul-Aug
Vol. 52
Issue 4
Pg. 201-6
ISSN: 1878-0849 [Electronic] Netherlands |
PMID | 19138766
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Complementary
- Dystroglycans
- DNA
- Mannosyltransferases
- protein O-mannosyltransferase
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Topics |
- Adolescent
- Alleles
- Base Sequence
- Child, Preschool
- DNA
(genetics, isolation & purification)
- DNA Mutational Analysis
- DNA, Complementary
- Dystroglycans
(metabolism)
- Female
- Humans
- Intellectual Disability
(genetics, pathology)
- Male
- Mannosyltransferases
(genetics)
- Molecular Sequence Data
- Muscle, Skeletal
- Muscular Dystrophies
(congenital, genetics, physiopathology)
- Muscular Dystrophies, Limb-Girdle
(genetics)
- RNA Splicing
- Sequence Analysis, DNA
- Sequence Deletion
(genetics)
- Severity of Illness Index
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