2008 Barcelona - European Society of Human Genetics

Normal variation, population genetics, genetic epidemiology
2006 AJMG 140A1617ff) .
Diagnosis of PA is generally established by in-depth testing with standardized
test batteries for visual cognition . As these time consuming
tests are not suitable for large scale screening, a questionnaire based
screening was introduced . In a pilot study in India and Hong Kong we
could show that only a few selected questions easily identify subjects
highly suspicious for PA (Kennerknecht et al . 2007, JHG 52:230ff) .
These tools were then applied at two Chinese Universities (Beijing
Normal University, Chang Chun Taxation College) . 2,000 questionnaires
with a five-point-rating scale for 21 test items regarding facial
and object recognition as well as some distractors were distributed .
Those students with the highest scores were then invited for diagnostic
interview . When starting with the highest scores, every 2nd student
was a prosopagnosic . Among a total of 40 students who scored above
2 S .D . more than 1/4 (n=11, 27 .5%) were prosopagnosics .
P07.107
A new approach concerning the registries for rare diseases
A. Tarniceru, M. Puiu, M. Serban;
University of Medicine and Pharmacy, Timisoara, Romania.
The registries for rare diseases follow to obtain epidemiological information
useful to understand the dimension of the problem . Knowing the
prevalence of rare diseases is an essential aspect for establishing the
most adequate methods for detection, prevention and management to
guide the health policy and the need for specialized personnel in different
regions . In addition the registries for rare diseases represent data
bases useful for research . It is necessary to ask for a well-informed
consent which will allow using the recorded data in registers and also
for future researches . The informed consent must be obtained after a
previous preparation and notification of the patient and/or his family. In
this way they will have all the information connected to the research in
which they are involved: results, risks, limits and benefits.
The registries for rare diseases have to be adapted, the criteria and
the tracking data have to be standardized in all European countries in
order to have as many cases possible . For this reason it is absolutely
necessary to create a new codification system approved by all countries,
which will encode all known rare diseases .
P07.108
Genetic characterization in 301 spanish Families Affected by
Autosomal Recessive Retinitis Pigmentosa
A. Avila-Fernandez, E. Vallespin, D. Cantalapiedra, R. Riveiro-Alvarez, J.
Aguirre-Lamban, A. Gimenez, M. Lopez-Martinez, I. Lorda-Sanchez, M. Trujillo-
Tiebas, C. Ayuso;
Fundacion Jimenez Diaz-CIBERER, Madrid, Spain.
Introduction . Retinitis pigmentosa (RP) is a genetically heterogeneous
disorder characterized by progressive loss of vision . We used a genotyping
microarray (Asper) to study proved or possible recessive cases
of RP, in order to optimise the molecular diagnosis of the disease .
Patients and Methods . 301 unrelated Spanish families containing 10
patients diagnosed as LCA, 96 as early onset Autosomal Recessive
Retinitis Pigmentosa (onset 10 years of age) . The families were also divided
by genetic classification (138 autosomal recessive cases and 163
sporadic cases) . All of them were analysed by a genotype microarray
specific for arRP (Asper), which tested more than 500 mutations in
16 recessive RP genes: CERKL, CNGA1, CNGB1, MERKT, PDE6A,
PDE6B, PNR, RDH12, RGR, PLBP1, SAG, TULP1, CRB1, RPE65,
USH2A and USH3A.
Results . No mutation was found in LCA group . The mutation frequency
was slightly higher in non early-onset (21,5%) than in early onset
(16,6%) families but these differences weren’t significatives. The allele
frequencies were: CERKL 2,9% (18/602), CNGA1 0,9% (6/602),
PDE6A 0,6% (4/602), PDE6B 0,3% (2/602), RLBP1 0,3% (2/602),
SAG 0,5% (3/602), CRB1 0,6% (4/602) and USH2A 7,8% (47/602) .
There weren’t significative differences between autosomal recessive
and sporadic cases .
Conclusion. The using of the genotype microarray is the first step in
molecular diagnosis in Spanish families with Autosomal Recessive
Retinitis Pigmentosa . USH2A is the main gene responsible followed
by p .Arg257ter mutation in CERKL gene in Spanish population . 95%
sporadic cases are inherited as an recessive form .
P07.109
RETN polymorphisms (−420C>G and IVS2+181G>A) in the
turkish population
N. Erginel-Ünaltuna 1 , M. Poda 1 , A. Onat 2 , N. Coban 1 , F. Guclu-Geyik 1 , G.
Can 3 ;
1 Istanbul University, DETAE, Genetics Dept., Istanbul, Turkey, 2 Turkish Cardiology
Association, Istanbul, Turkey, 3 Istanbul University, Cerrahpasa Medical
Faculty, Dept. of Public Health, Istanbul, Turkey.
Resistin hormone (RETN) plays an important role in the insulin resistance
mechanism . The effects of the two variants in the resistin
gene (RETN −420C>G and IVS2+181G>A) on metabolic syndrome
and cardiovascular events have been studied in the Turkish population
. 208 healthy individuals, 360 with metabolic syndrome and 75
subjects with heart disease were genotyped . The genotype and allele
frequencies of the RETN polymorphisms in the Turkish population
have been determined for the −420C>G (CC: 47%, GC: 44%, GG: 9%)
and IVS2+181G>A (GG: 52%, GA: 39%, AA: 9%) polymorphisms . The
genotype and allele distributions have been found to be similar to other
Europen populations .
In our study group the IVS2+181AA genotype has been found to
be associated with low HDL-cholesterole levels (p=0 .035) . The AA
genotype and dyslipidemia showed an association in both obese
(p=0 .012) and non-obese men (p=0 .016) . In the obese group, the carriers
of IVS2+181AA and AG genotypes had higher trigliceride levels
(p=0 .044) than the GG genotype . In men, higher triglyceride levels
have been associated to -420GG genotype (p=0 .029) . Furthermore, in
obese men, the -420GG genotype has also been associated with dyslipidemia
(p= 0 .036) . On the other hand, the IVS2+181A (p=0 .0001)
and -420G (p=0 .009) allele carriers had lower log folate levels in the
whole study population .
This study indicates that the variations in the RETN gene (−420C>G
ve IVS2+181G>A) may effect lipid and the folate levels . Particularly,
dyslipidemia was present more frequently in IVS2+181AA and -420GG
genotype-carrying obese men, hence they may further contribute to
MI risk .
P07.110
the Bayash Roma: phylogenetic dissection of Eurasian paternal
genetic elements
I. Martinovic Klaric, M. Pericic Salihovic, L. Barac Lauc, B. Janicijevic;
Institute for Anthropological Research, Zagreb, Croatia.
The Bayash consist of numerous and small Romani groups speaking
different dialects of the Romanian language and living dispersedly in
Croatia, Hungary, Bosnia and Herzegovina, Serbia, Romania, Bulgaria,
and to the lesser extent in Macedonia, Greece, Ukraine, Slovakia
and Slovenia . Larger Bayash groups migrated to Croatia most likely
during the 19th century, after abolition of slavery in Romania . Molecular
architecture and the origin of the Croatian Bayash paternal gene
pool was addressed by analysing 151 Bayash Y chromosomes from
two Croatian regions, 332 Y chromosomes from Romani populations
across Europe, 814 Y-chromosomes from non-Romani host populations
living in Southeastern, Southern and Eastern Europe as well as
with 1680 Y-chromosomes from South Asian populations . The Bayash
in Croatia represent one population of largely shared paternal genetic
history characterized by substantial percentage (44%) of common H1-
M82 and E3b1-M78 lineages . Relatively ancient expansion signals
and limited diversity of Indian specific H1-M82 lineages imply descent
from closely related paternal ancestors who could have been settled
in the Indian subcontinent between 7 th and 9 th centuries AD . Minimal
time divergence of the Bayash subpopulations is consistent with their
putative migratory split within Romania towards Wallachia and Transilvania
. Substantial percentage of E3b1 lineages and high associated
microsatellite variance in the Bayash men is a reflection of significant
admixture with majority populations from the Vardar-Morava-Danube
catchment basin - possibly a common paternal signature of Romani
populations in Southeastern Europe . Additional traces of admixture
are evident in the modest presence of typical European haplogroups .