ISSN 10227954, Russian Journal of Genetics, 2012, Vol. 48, No. 8, pp. 838–845. © Pleiades Publishing, Inc., 2012.
Original Russian Text © V.V. Zabnenkova, E.L. Dadali, M.G. Spiridonova, R.A. Zinchenko, A.V. Polyakov, 2012, published in Genetika, 2012, Vol. 48, No. 8, pp. 983–992.
Proximal spinal muscular atrophy (SMA) is the
most prevalent hereditary disease causing early child
death; its incidence rate is between 1 : 6000 and 1 :
10000 newborns [1, 2].
Spinal muscular atrophy is an autosomal recessive
neuromuscular disease leading to progressive myas
thenia and atrophy of proximal muscles .
Sixty percent of SMA patients have the most severe
form of the disease, type I SMA also called Werdnig–
Hoffman disease. Type I SMA is characterized by an
early onset (under six months) and death of respiratory
failure under an age of two years [4, 5].
Type II SMA manifests itself at an age of 6–
18 months and is characterized by a more benign
progress. The affected children retain the ability to sit
without aid. The mean life expectancy is 10–14 years
The age at onset of type III SMA or Kugelberg–
Welander syndrome varies between 18 months and the
first to second decade of life. Type III SMA patients
retain the ability to walk [4, 5].
An adult form of the disease, type IV SMA, has also
been described. This disease first manifests itself dur
ing the third decade of life; it is characterized by a
latent onset and slow progress [4, 5].
A mutation (telomeric copy) in the
encoding the survival of motor neuron (SMN) protein
is the molecular genetic cause of SMA . The gene is
located in the 5q13 locus of the chromosome 5 dupli
cation region and has an almost identical homolog,
gene (a centromeric copy) . More than
90% of the total amount of a functionally active SMN
protein is expressed from the
only insignificantly contributing to the production of
the fullsize SMN protein fraction. This is determined
by a point substitution in exon 7, which is one of five
differences between the telomeric and centromeric
copies of the SMN gene. This substitution alters the
exon splicing enhancer site, thus interfering with nor
mal posttranscriptional processing [8, 9].
The numbers of the
vary in different individuals within a population .
Individuals without SMA may carry from two to
gene copies. According to published data,
85–95% of people carry one
copy in each chro
mosome 5 [10, 11].
Most SMA patients (95%) have no
The remaining 5% are compound heterozygotes with
a deletion of the
gene in one chromosome 5 and
gene with a point mutation or small dele
tions or insertions in the other one .
In addition, cases of asymptomatic SMA have been
described, with a patient being homozygous for an
gene deletion but also carrying more than three
copies of the
gene, which partly or completely
compensates for the absence of the
Most heterozygous carriers of SMA have one copy
Heterozygous Carrier Rate for Type I–IV Proximal Spinal Muscular
Atrophy in Chuvashes, Udmurts, and Residents
of the Moscow Region
V. V. Zabnenkova
, E. L. Dadali
, M. G. Spiridonova
, R. A. Zinchenko
, and A. V. Polyakov
Medical Genetic Research Center, Russian Academy of Medical Sciences, Moscow, 115478 Russia
Research Institute of Medical Genetics, Siberian Branch, Russian Academy of Medical Sciences, Tomsk, 634050 Russia
Received October 18, 2011
—The first estimation of the heterozygous carrier rates for the
gene deletions and
duplications in populations of Russia has been performed. The numbers of
gene copies have been deter
mined in samples from Chuvash and Udmurt populations, as well the population of the Moscow region, by
means of multiplex ligationdependent probe amplification. The heterozygous carrier rates for the
were 2.7% (1 : 37 people), 2.8% (1 : 36 people), and 2.8% (1 : 36 people) in Chuvashes, Udmurts, and resi
dents of the Moscow region, respectively. The
duplication frequencies have been determined in the
studied groups. It is 1.5, 4, and 2.5% in Chuvashes, Udmurts, and residents of the Moscow region, respec
tively. The high
duplication frequency in Udmurts may explain why the
frequency in this population was overestimated in earlier PCR–RFLP analyses.