2009 Vienna - European Society of Human Genetics

Evolutionary and population genetics, and Genetic epidemiology
predisposition to lymphoid tumors. Most of the NBS patients are of
Slavic origin and carried a major founder mutation 657del5 of the NBN
gene. The prevalence of the 657del5 in the West Ukraine was previously
studied by R. Varon et al. (2000) and frequency of heterozygotes
was estimated as 1:182, expected NBS cases - 1:133 000. Since 1999
and till 2009 the 30 NBS cases were diagnosed in Ukraine, half of
them - in the Lviv region of the West Ukraine. The purpose of this study
was to evaluate the prevalence of 657del5 mutation of the NBN gene
in Lviv population upon a base of verified NBS cases. The total number
of 511598 children were born in Lviv region in 1989-2007 years and
11-years period was marked by NBS case appearance: 1989 (1), 1990
(1), 1992 (2), 1994 (1), 1998 (2), 2001 (1), 2002 (1), 2003 (2), 2004
(1), 2005 (1), 2007 (2). Thus, in the time span of 2 years, 1-2 new NBS
cases are expected to be born. The frequency of Nijmegen breakage
syndrome in Lviv population is estimated as 1 per 13640-34106 neonates,
whereas the prevalence of 657del5 heterozygotes is approximately
1 per 58-95 neonates. The high frequency of heterozygous
carriers of NBN founder mutation in Lviv population may contribute to
cancer frequency in the West Ukraine.
P10.65
the spectrum of GJB2 (connexin-26) mutations in patients
with nonsyndromic hearing loss: high prevalence of the allelic
variant V37i (109G>A) in Asian populations of sakha (Yakutia)
N. A. Barashkov 1 , L. U. Dzhemileva 2 , S. A. Fedorova 1 , F. M. Terutin 3 , E. E.
Fedotova 3 , E. K. Khusnutdinova 2 ;
1 Yakut Scientific Centre of Complex medical problems, Siberian Branch of
Russian Academy of Medical Sciences, Yakutsk, Russian Federation, 2 Institute
of Biochemistry and Genetics, Ufa Research Centre, Russian Academy of Sciences,
Ufa, Russian Federation, 3 Republican Hospital №1 – National Centre of
Medicine, Yakutsk, Russian Federation.
Congenital hearing loss is one of the frequent sensory defects affecting
1-3 in 1000 newborns, and 50% of these cases are hereditary determined.
Nonsyndromic hearing loss (NSHL) accounts approximately
80% of hereditary deafness cases. GJB2 mutations are implicated as a
major cause for the development of NSHL in majority of populations.
We studied GJB2 mutation spectrum in patients with NSHL in Sakha
Republic (Yakutia) (East Siberia, Russia). A total of 66 patients with
NSHL of different ethnic affiliation (Caucasians and Asians) were analyzed
by PCR-SSCP and further sequencing of GJB2 gene. The molecular
screening of V37I in 6 populations of Yakutia (Yakuts, Dolgans,
Evenks, Evens, Yukaghirs and Russians) was performed using allelespecific
amplification PCR method.
GJB2 mutations were found in 50.0% of Caucasian and 9.2% of Asian
patients chromosomes. We identified 3 different deletions 35delG,
312del14, 333-334delAA known as recessive and 5 different missense
mutations V27I, M34T, V37I, R127H, E114G which pathogenic role is
controversial. One of the common allelic variants in Asian patients is
V37I (45% of all mutant chromosomes). Molecular screening of V37I
in 6 populations of Yakutia showed that it was one of the common
allelic variant in studied populations. We found the V37I allele in Turkic-speaking
populations of Yakuts, Tungusic-speaking populations of
Evenks and Evens and Slavic-speaking ones of Russians. V37I was
not detected in populations of Dolgans and Yukaghirs. High prevalence
of V37I in populations of Yakutia may be a result of common
founder effect.
This work was supported by RFBR (08-04-90730) and RHSF (08-06-
84602a/U).
P10.66
the comparative analysis of hereditary skeletal disorders’
spectrum in Rostov region
R. A. Valkov 1 , S. S. Amelina 2 , R. A. Zinchenko 3 ;
1 Railroad clinical hospital, Rostov-on-Don, Russian Federation, 2 Rostov regional
clinical hospital, Rostov-on-Don, Russian Federation, 3 Research Centre
for Medical Genetics, Russian Academy of Medical Sciences (RCMG RAMS),
Moscow, Russian Federation.
Hereditary skeletal disorders (HSD) are a large heterogeneous group
of genetic diseases with different prevalence rate in populations. A
cumulative international incidence of at least 1:5000 newborns has
been estimated (in most cases, it was estimated by cumulating information
from the different publications). The following ten syndromes:
Marfan syndrome - 30:100,000; Arthrogryposis multiplex congenita
- 30:100,000; Polydactyly, preaxial - 25:100,000; Syndactyly, type 1
- 25:100,000; Ehlers-Danlos syndrome, type 3 - 12.5:100,000; Osteogenesis
imperfecta - 6.5:100,000; Achondroplasia - 4.5:100,000;
Epiphyseal dysplasia multiple - 5:100,000; Acrocephalosyndactyly
- 4.6:100,000; Diastrophic dwarfism - 3.5:100,000 were the most
frequent HSD (isolated and syndromic forms) in the world. 320925
people of eight areas of Rostov region were examined. The research
was made taken under the RCMG RAMS protocol, which, according
to OMIM, provides more than 2500 genetic diseases diagnosis.
Then families with HSD were selected from the cite data. In the results
336 patients from 226 families were detected with HSD. The total
prevalence rate of HSD in Rostov region was 1:950. The following ten
syndromes: Ehlers-Danlos syndrome, type 3 - 15.6:100,000; Marfan
syndrome - 5:100,000; scoliosis, idiopathic - 5:100,000; Polydactyly,
postaxial - 4.7:100,000; Noonan syndrome - 4:100,000; Syndactyly,
type 1 - 3.7:100,000; Osteogenesis imperfecta - 3.1:100,000; Achondroplasia
- 2.8:100,000; Syndactyly, type 2 - 2.8:100,000; Polydactyly,
preaxial - 2.5:100,000 were the most frequent HSD in the Rostov region.
Diversity and incidence of the most frequent HSD differs from the
world data. The further research will enable to reveal the reasons of
this regional HDS spread peculiarities.
P10.67
Epidemiological aspects of Osteogenesis imperfecta in
Bashkortostan Republic of Russia
D. Nadyrshina1 , R. Khusainova1 , A. Mardanova2 , E. Khusnutdinova1 ;
1 2 Institute of Biochemistry and Genetics RAS, Ufa, Russian Federation, Republic
Perinatal Centre, Ufa, Russian Federation.
Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous
disorder of connective tissue characterized by brittle bones, blue
sclerae, short stature, bone deformity, hearing loss and dentinogenesis
imperfecta. 95 patients with OI are identified from 90 families the
Republic of Bashkortostan (RB). The prevalence of OI is estimated at
1 per 45000, whereas in other countries of the world it is estimated to
be 1:10000-1:30000. Our results show that OI is extended irregularly
in the RB. The disease is detected in 29 from 54 administrative districts
and in 12 from 21 cities. The incidence of OI varies from 0.42:100000
to 17.8:100000. The distribution of patients by the sex composition
is as follows 52males and 43 females. Epidemiological investigations
based on the ethnic composition of 95 patients with OI scattered are
as follows: Tatars -29.4%, Russians- 23.1%, Bashkirs - 18.9%, 6.2%
from Armenians, Maris, Ukrainians, Chuvashes and 22.4% are metis.
70 from 95 cases have blue sclera (34males and 36females). 16
patients have autosomal dominant and 79 have autosomal recessive
inheritance pattern. More than 10 fractures during their lifetime had 39
patients, multiple fractures - 33 patients and 23 patients didn`t have
fractures. The distribution of patients with OI by the age composition is
congenital 22 cases (26%), from 1 to 7 years old 35 patients (42.8%)
and from 8 and older 27 cases (32.3%). The irregular prevalence of OI
in RB, apparently, occurs randomly as absence of patterns associated
with local concentration incidents with OI.
P10.68
study of two common P53 gene mutations in gastric cancer
using (PcR-RFLP) in a Province of iran
J. Saffari Chaleshtori 1 , M. Moradi 2 , E. Farrokhi 2 , M. Tabatabaieefar 2 , M. Taherzadeh
Ghahfarrokhi 1 , G. Mobini 2 , S. Khademi 2 , F. Shayesteh 2 , M. Shahrani 2 , G.
Mardani 2 , M. Banitalebi 2 , N. Parvin 2 , N. Shahinfar 2 , G. Rahimian 2 , H. Nazem 3 ,
M. Hashemzadeh Chaleshtori 2 ;
1 Payame Noor Univ. Tehran & Cellular and Molecular Research Center
Shahrekord Univ. of Med.Sci. Iran, Shahrekord, Islamic Republic of Iran,
2 Cellular and Molecular Research Center Shahrekord Univ. of Med.Sci. Iran,
Shahrekord, Islamic Republic of Iran, 3 Payame Noor Univ. Tehran, Shahrekord,
Islamic Republic of Iran.
Background and aim: Gastric cancer is the most common cause of
cancer death world wide after lung cancer. Genetic factors including
oncogenes and tumor suppressor genes are always involved in progression
of this cancer. The P53 tumor suppressor gene is believed
to have a broad role in the cell such as programmed cell death and
stop cell replicating damaged DNA which has been summarized on the
guardian of the genome. This study aims to determine the frequency of
two common P53 gene mutations using PCR-RFLP in gastric cancer
in a Province of Iran