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Proximal myotonic myopathy: clinical and molecular investigation of a Norwegian family with PROMM
Author(s) -
Sun Chen,
Henriksen Olaf Anton,
Tranebjærg Lisbeth
Publication year - 1999
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.1999.560609.x
Subject(s) - proband , genetics , locus (genetics) , myotonia , myotonic dystrophy , genetic linkage , myopathy , locus heterogeneity , haplotype , biology , genetic heterogeneity , gene , allele , mutation , phenotype
Proximal myotonic myopathy (PROMM) was first described in 1994 as a multisystem disorder with similarity to myotonic dystrophy (DM), but without the abnormal (CTG) n expansion in the DM protein kinase (DMPK) gene. The inheritance is autosomal dominant and the clinical features include myotonia, proximal muscle weakness and cataract. Linkage analysis in nine German PROMM families has indicated the possibility of linkage to DM2 locus on chromosome 3. We report a Norwegian PROMM family in which the proband was clinically diagnosed as DM but without the (CTG) n expansion. Using an intragenic marker we showed that the DMPK gene did not segregate with the disease in this family. All family members are heterozygous for the R894X mutation in CLCN1 gene. Linkage analysis could not be performed, but haplotyping probably excludes the DM2 locus as the disease locus in this family. The present family emphasises that myalgia is a prominent symptom in PROMM and the clinical differences may be explained by genetic heterogeneity. This family will be reinvestigated along with the identification of candidate genes or regions in larger PROMM families.