ISSN 10227954, Russian Journal of Genetics, 2015, Vol. 51, No. 7, pp. 695–701. © Pleiades Publishing, Inc., 2015.
Original Russian Text © A.N. Semyachkina, T.A. Adyan, M.N. Kharabadze, P.V. Novikov, A.V. Polyakov, 2015, published in Genetika, 2015, Vol. 51, No. 7, pp. 812–820.
Marfan syndrome is a monogenic connective tissue
disease that is common and is observed by doctors in
various fields: pediatricians, therapists, cardiologists,
surgeons, ophthalmologists, orthopaedics, etc. The
disease is characterized primarily by the disturbance of
the cardiovascular system, the muscular skeletal appa
ratus, and the visual organ.
Significant clinical polymorphism of the pathol
ogy, which involves many vital organs and body sys
tems, variability in the disease manifestation periods,
and phenotypic similarity with other hereditary syn
dromes often produce great problems for doctors in
achieving timely diagnostics.
Marfan syndrome is often first diagnosed at autop
sies associated with aorta disruption due to an aneu
rysm that was not revealed during the patient’s life.
Probands with Marfan syndrome frequently follow up
continuously with “narrow specialists” and are diag
nosed with lens subluxation, funnel or pigeon chest
deformation, kyphoscoliosis, etc.
The timely diagnosis of Marfan syndrome is very
important for correct patient treatment, disability pre
vention, and improvement of the quality and longevity
of life, as well as for the efficient medical and genetic
consultation based on direct DNA diagnostics of the
Williams originally described Marfan syndrome in
1876. The disease was named for the French pediatri
cian Antuan Marfan, who followed a fiveyearold girl
with typical symptoms of the disease for 20 years.
The frequency of Marfan syndrome, according to
Orphanet (2014), is 20 in 100 thousand subjects .
The disease was observed everywhere and in all ethni
The disease is inherited in the autosomal dominant
type with high penetration ability of the mutant gene
. The majority of the disease cases (75%) are fam
ilyrelated, while 25% occur sporadically due to pri
mary gene mutation.
Marfan syndrome is governed by mutations in the
1 gene, which is localized on the long arm of
chromosome 15 at the locus 15q21.1. The first muta
tions in this gene in Marfan syndrome patients were
revealed in 1991 .
1 gene product is the glycoprotein fibril
lin1. Its molecular mass is 320 kDa. The protein is
synthesized initially in the form of profibrillin1. It
consists of 2871 amino acids. Profibrillin1 is then
subjected to proteolytic processing and is trans
formed to fibrillin1. Profibrillin1 is not part of the
extracellular matrix of the connective tissue unless it
is converted into fibrillin1. It has been proven that
fibrillin1 has a significant importance for the correct
Clinical and Genetic Characteristics of Russian Marfan Patients
A. N. Semyachkina
, T. A. Adyan
, M. N. Kharabadze
, P. V. Novikov
, and A. V. Polyakov
Research Institute for Clinical Pediatrics, Pirogov National Research Medical University, Moscow, 125412 Russia
Research Center for Medical Genetics, Russian Academy of Medical Sciences, Moscow, 115478 Russia
Received August 19, 2014; in final form, January 26, 2015
—The results of direct DNA diagnostics in nine patients with Marfan syndrome, aged from two to
52 years old, and four unhealthy relatives with the same disease from two unrelated families have been presented
for the first time in Russia. Eight mutations in the gene
1 were revealed. One patient demonstrated a sub
stitution with unknown clinical importance, which was previously described in the SNP database as
rs112287730 with a frequency of incidence of 0.1%. Out of the eight mutations, two (25%) were previously
described, and the other six mutations (75%) were revealed for the first time. These mutations revealed by us
were of the following types: three mutations (37.5%) produced a shift in the open reading frame (two deletions
and one insertion), three mutations (37.5%) involved a splicing site, and one (12.5%) nonsense mutation was
also noted. Our data contradict previous reports that claimed that the majority of mutations in the
represented missense mutations. Such inconsistency could result from a small size of the examined sample or
from substitutions that produced alteration in the splicing site (as we have demonstrated here). The distribution
of the revealed mutations was uniform along the whole gene. The results of the conducted comparative analysis
of genetic and phenotypic indices was in complete agreement with previously reported results. The developed
direct method of DNA diagnostics was fully informative, as we managed in all nine examined patients to con
firm their clinical diagnosis using a molecular and genetic approach.