Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-01, Vol.89 (2), p.623-627
• Main Authors: BEGGS, A. H, NEUMANN, P. E, ARAHATA, K, ARIKAWA, E, NONAKA, I, ANDERSON, M.-D. S, KUNKEL, L. M
• Format: Article
• Language: English
• Subjects: 550400 - Genetics; Abnormalities, Multiple - genetics; ANIMALS; ASIA; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; Blotting, Western; Chromosome Deletion; CHROMOSOMES; DEVELOPED COUNTRIES; DISEASES; Diseases of striated muscles. Neuromuscular diseases; DNA; dystrophin; Dystrophin - genetics; ELECTROPHORESIS; EPIDEMIOLOGY; Gene Expression; Genes; Genes, Recessive; Genetic Linkage; Genetics; HEREDITARY DISEASES; HETEROCHROMOSOMES; Heterozygote; HUMAN CHROMOSOMES; HUMAN POPULATIONS; HUMAN X CHROMOSOME; Humans; JAPAN; Male; MALES; MAMMALS; MAN; Medical sciences; MEN; MOLECULAR BIOLOGY; MUSCLES; Muscular Dystrophies - genetics; Muscular Dystrophies - pathology; Muscular dystrophy; MUTATIONS; NERVOUS SYSTEM DISEASES; Neurology; NUCLEIC ACIDS; ORGANIC COMPOUNDS; PATIENTS; Phenotype; POPULATIONS; PRIMATES; RECESSIVE MUTATIONS; SEX RATIO; VERTEBRATES; X CHROMOSOME
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.2.623

Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, we propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative to Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.