J Med Genet 1999;36:62-64
( January )
Short report
Unstable expansion of the CAG trinucleotide repeat in MAB21L1:
report of a second pedigree and effect on protein expression
Russell L Margolisa, O Colin Stineb, Christopher M Warda, Mary L Franza, Adam Rosenblatta, Colleen Callahana, Meeia Sherra, Christopher A Rossa c, Nicholas T Potterd
a Division of
Neurobiology, Department of Psychiatry and Behavioral Science, Johns
Hopkins University School of Medicine, Baltimore, MD, USA, b Department of Pediatrics, University of Maryland
School of Medicine, Baltimore, MD, USA, c Department of Neuroscience, Johns Hopkins
University School of Medicine, Baltimore, MD, Program in Cellular and
Molecular Medicine, Johns Hopkins University School of Medicine,
Baltimore, MD, USA, d Developmental
and Genetic Center, The University of Tennessee Medical Center,
Knoxville, TN, USA
Correspondence to: Dr Margolis, Department of Psychiatry, Meyer 2-181, 600 N Wolfe Street,
Baltimore, MD 21287, USA.
Received 7 May 1998;
Revised version accepted for publication 17 June 1998
MAB21L1, originally termed CAGR1, is the human homologue
of the C elegans cell fate determining gene
mab21. MAB21L1, mapped to
13q13, contains a highly polymorphic 5' untranslated CAG repeat that
normally ranges from six to 31 triplets in length. A pedigree has been
previously reported in which the repeat length is expanded to 45-50 triplets and is transmitted unstably between generations; the expansion
did not correlate to a clinical phenotype but did exhibit somatic
mosaicism. We now report a second pedigree with an expanded and
unstably transmitted MAB21L1 CAG repeat of similar length. The
expansion is not clearly associated with a clinical phenotype, though
the complexity of the pedigree renders any conclusion concerning
phenotype-genotype relationships speculative. The expansion did not
result in decreased expression of MAB21L1 protein. The length, C-G rich
composition, somatic mosaicism, and unstable transmission of the
expanded CAG repeat in MAB21L1 resemble the premutations observed in
other genes, such as FMR1 and MDPK, in which longer expanded repeats
are associated with a clinical phenotype. This raises the possibility
that longer expansions in the MAB21L1 repeat may also be associated
with a clinical phenotype.
Keywords:
trinucleotide;
repeat;
expansion;
MAB21L1
© 1999 by J Med Genet
