title: The genes encoding for D4Z4 binding proteins HMGB2, YY1, NCL, and MYOD1 are excluded as candidate genes for FSHD1B.
abstract: Facioscapulohumeral muscular dystrophy is a disease of skeletal muscle, with symptoms including both facial and shoulder girdle weakness and progression to involve the pelvic girdle and extremities in the majority of cases. For most cases of FSHD, the molecular basis of the disease can be identified as a partial deletion of the D4Z4 repeat array on the end of the long arm of chromosome 4. However, in up to 5% of FSHD families there is no linkage to 4q35. These cases are designated as FSHD1B. Proteins have been identified that bind to the D4Z4 repeats of chromosome 4q35. The genes encoding D4Z4 binding proteins YY1, HMGB2, NCL, and MYOD1 were investigated as candidate genes for FSHD1B. Coding sequences and promoter region were analyzed for HMBG2 and no sequence variations were detected. For YY1, all five exons were analyzed and a polymorphism was detected in both the unaffected and affected populations. In nucleolin (NCL), several SNPs were identified, including a SNP causing the non-synonymous change P515H; however, all polymorphisms either occurred in control samples or were previously reported. A novel polymorphism was also detected in MYOD1, but did not represent a disease-specific variation. These results suggest that HMBG2, YY1, NCL, and MYOD1 are unlikely to represent the genes responsible for FSHD in these families.
authors.affiliation: Center for Human Genetics, Duke University Medical Center, 595 LaSalle Street, Box 3445, Durham, NC 27710, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Bastress
authors.forename: J M
authors.initials: JM
authors.lastname: Stajich
authors.forename: M C
authors.initials: MC
authors.lastname: Speer
authors.forename: J R
authors.initials: JR
authors.lastname: Gilbert
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002894:Chromosomes, Human, Pair 4; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D005091:Exons; D005192:Family Health; D024261:HMGB2 Protein / Q000235:genetics*; D006801:Humans; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics*; D017570:MyoD Protein / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D050986:YY1 Transcription Factor; D000097796:Nucleolin
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D024261:HMGB2 Protein; D017570:MyoD Protein; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D000097796:Nucleolin; C057363:MyoD1 myogenic differentiation protein; C494698:YY1 protein, human