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

Journal Article · Wed Jan 15 00:00:00 EST 1992 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.89.2.623· OSTI ID:5558867

Beggs, A H; Neumann, P E; Anderson, M S; Kunkel, L M ^[1]; Arahata, Kiichi; Arikawa, Eri; Nonaka, Ikuya ^[2]

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1. Harvard Medical School, Boston, MA (United States)
2. National Inst. of Neuroscience, Tokyo (Japan)

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 1/3,500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, the authors 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.

• OSTI ID: 5558867
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 89:2; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DNA
ELECTROPHORESIS
HEREDITARY DISEASES
MOLECULAR BIOLOGY
EPIDEMIOLOGY
HUMAN POPULATIONS
HUMAN X CHROMOSOME
JAPAN
MEN
MUSCLES
NERVOUS SYSTEM DISEASES
PATIENTS
RECESSIVE MUTATIONS
SEX RATIO
ANIMALS
ASIA
CHROMOSOMES
DEVELOPED COUNTRIES
DISEASES
HETEROCHROMOSOMES
HUMAN CHROMOSOMES
MALES
MAMMALS
MAN
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
POPULATIONS
PRIMATES
VERTEBRATES
X CHROMOSOME
550400* - Genetics