Association between Agl-CA alleles and severity of autosomal recessive proximal spinal muscular atrophy

Christine J. DiDonato, Kenneth Morgan, John D. Carpten, Paul Fuerst, Susan E. Ingraham, Gary Prescott, John D. McPherson, Brunhilde Wirth, Klaus Zerres, Orest Hurko, John J. Wasmuth, Jerry R. Mendell, Arthur H M Burghes*, Louise R. Simard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


The gene for autosomal recessive proximal spinal muscular atrophy (SMA) has been mapped to an 850-kb interval on 5q11.2-q13.3, between the centromeric D5S823 and telomeric D5S557 markers. We report a new complex marker, Ag1-CA, that lies in this interval, whose primers produce one, two, or rarely three amplification-fragment-length variants (AFLVs) per allele. Class I chromosomes are those which amplify a single AFLV allele, and class II chromosomes are those which amplify an allele with two or three AFLVs. Ag1-CA shows highly significant allelic association with type I SMA in both the French Canadian (Hôpital Sainte-Justine [HSJ]) and American (Ohio State University [OSU]) populations (P<.0001). Significant association between the Ag1-CA genotype and disease severity was also observed. Type I patients were predominantly homozygous for class I chromosomes (P=.0003 OSU; P=.0012 HSJ), whereas the majority of type II patients were heterozygous for class I and II chromosomes (P=.0014 OSU; P=.001 HSJ). There was no significant difference in Agl-CA genotype frequencies between type III patients (P=.5 OSU; P=.25 HSJ) and the paired normal chromosomes from both carrier parents. Our results indicate that Ag1-CA is the most closely linked marker to SMA and defines the critical candidate-gene region. Finally, we have proposed a model that should be taken into consideration when screening candidate SMA genes.

Original languageEnglish (US)
Pages (from-to)1218-1229
Number of pages12
JournalAmerican journal of human genetics
Issue number6
StatePublished - Dec 1994

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Association between Agl-CA alleles and severity of autosomal recessive proximal spinal muscular atrophy'. Together they form a unique fingerprint.

Cite this