European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Genetic analysis, linkage, and association
P1047. N-acetyltransferase 2 (NAT2) gene polymorphisms
in psoriasis and colon cancer patients from the Moscow
population
Z. M. Kozhekbaeva 1 , O. A. Gra 2 , A. S. Glotov 3 , I. V. Goldenkova-Pavlova 1 , S.
A. Bruskin 1 , E. V. Markarova 4 , E. S. Piruzyan 1 , T. V. Nasedkina 2 ;
1 Vavilov Institute of General Genetics RAS, Moscow, Russian Federation,
2 Engelhardt Institute of Molecular Biology RAS, Moscow, Russian Federation,
3 Ott’s Institute of Obstetrics and Gynecology RAMS, Saint-Petersburg, Russian
Federation, 4 Center of Theoretical Problems of Physical and Chemical Pharmacology
RAS, Moscow, Russian Federation.
N-acetyltransferase 2 (NAT2) is one of the key enzymes of a phase II
detoxification of xenobiotics, including carcinogens. The decrease in
activity of NAT2 enzyme may correlate with accumulation of harmful
intermediate metabolites and influence on the risk to develop different
multifactorial diseases. NAT2-biochip has been developed including
17 SNP in the NAT2 gene, most significant for European populations
(282C/T, 341T/C, 481C/T, 590G/A, 803A/G and 857G/A). The biochip
has been tested on more than 450 clinical DNA samples of 166 patients
with psoriasis, 104 patients with rectal cancer, 84 patients with
various dermatological diseases and 99 healthy individuals. We found
that patients with psoriasis and rectal cancer had the increased frequency
of mutation 282T comparing with population control (OR=1.3,
p = 0.134 and OR = 1.58, p = 0.045, respectively). On the contrary, the
mutation 481T had a reduced frequency in patients with psoriasis comparing
with healthy controls (OR=0.89, p = 0.567). No differences have
been found in distribution of the same mutations in male and female.
Also patients with psoriasis and rectal cancer revealed the increase in
frequency of 590A mutation in comparison with control group (OR =
1.48, p = 0.055 and OR = 1.501, p = 0.0656, respectively). Thus, the
data presented suggest association of separate polymorphic variants
of gene NAT2 with such multifactorial diseases as psoriasis and rectal
cancer.
The work has been particularly supported by a grant „Fundamental
Science for Medicine“ from the Presidium of the Russian Academy of
Sciences.
P1048. A new substitution in Aqp2 gene in a family with history
of three affected children with Nephrogenic Diabetes Insipidus
N. Almadani 1 , V. Hadavi 1 , F. Afroozan 1 , R. Kariminejad 1 , D. G. Bichet 2 , H.
Najmabadi 1 ;
1 Kariminejad-Najmabadi Pathology & Genetics Center, 14665/154, Tehran,
Islamic Republic of Iran, 2 Universite de Montreal,Hopital du Sacre-Coeur de
Montreal, Montreal, PQ, Canada.
Nephrogenic diabetes insipidus (NDI) is characterized by inability to
concentrate the urine, which results in polyuria (excessive urine production)
and polydipsia (excessive thirst). NDI is most commonly inherited
in an X-linked manner (~90% of individuals), but can also be
inherited in an autosomal recessive manner (~9% of individuals) or in
an autosomal dominant manner (~1% of individuals). Autosomal NDI is
caused by mutation in the gene encoding the aquaporin-2 water channel
(Aqp2), which maps to chromosome 12q13.We report on a family
with history of two daughters and a son affected with Nephrogenic diabetes
insipidus, who developed the clinical and biochemical features
of metabolic acidosis and hypernatremic dehydration with generalized
hypotonia and moderate mental retardation in the first year of life. They
suffered from unconsiousness spell, polyuria and polydypsia without
any ophthalmologic cystinosis. Laboratory tests indicated severe anemia,
asotemia, thrombocytopenia and they died from the disease in
the first 5 years of life.We determined by sequencing analysis that the
two parents were both heterozygote for the G175R mutation in Aqp2
gene. The mutation is already known but the base pair change is new.
It is thus likely that the deceased infants were homozygotes for this
mutation and suffered from repeated episodes of dehydration due to
non-linked Nephrogenic diabetes insipidus. The prenatal diagnosis for
this family revealed that the fetus was heterozygote for the same mutation.
P1049. MGP gene T-138C and G-7A polymorphisms in patients
with nephrolithiasis.
A. Kizilyer 1 , A. Arslan 1 , B. Göğebakan 1 , M. İğci 1 , S. Erturhan 2 , Y. İğci 1 , S.
Oğuzkan 1 , E. A. Çakmak 1 , H. Şen 2 ;
1 Department Medical Biology and Genetics, Gaziantep, Turkey, 2 Department of
Urology, Gaziantep, Turkey.
Kidney stone formation is the result of cascade of events to mineralize
calcium salts in the urinary space causing pathological nephrolithiasis
condition. The mechanism of nephrolithiasis is unknown and usually
calcification and stone formation is associated with the bone specific
proteins. One of them is human matrix Gla protein (MGP). It is also
shown that calcium containing stone growth concurs with the increase
of MGP expression along with the other proteins. MGP gene is located
on chromosome 12p13.1 - p12.3, consists of 4 exons. Its promoter
region contains dense binding sites for variety of transcription factors.
In addition to T-138C and G-7A polymorphisms, primer design for the
analysis of promoter sites has been achieved using Workbench Biology
3.2. Promoter screening and polimorphic analysis were done
by SSCP and PCR-RFLP methods using NcoI and BsrSI restriction
enzymes. For this, 89 patients with familial and 111 patients with sporadic
nephrolithiasis, totalling 200 neprolithiasis patients and 94 normal
subject DNAs from their peripheral blood samples were used. The
results showed that there is no significant difference between patient
and control groups for T-138C and G-7A polymorphisms. Therefore,
no association can be attributed to T-138C and G-7A polymorphisms
in patients with nephrolithiasis.
P1050. No evidence of Neuregulin 1 plays a role in the
continuum model of psychosis
N. Unlu-Gursoy 1 , Z. Yuncu 2 , B. Akin 3 , M. Celik 1 , S. Kesebir 4 , S. Vahip 5 , A.
Ulusahin 1 , N. A. Akarsu 3 ;
1 Hacettepe University, Department of Psychiatry, Ankara, Turkey, 2 Ege University,
Department of Child Psychiatry, Izmir, Turkey, 3 Hacettepe University,
Department of Pediatrics, Gene Mapping Laboratory, Ankara, Turkey, 4 State
Hospital, Psychiatry Unit, Kirikkale, Turkey, 5 Ege University, Department of
Psychiatry, Izmir, Turkey.
Although family and twin studies support independent transmission of
schizophrenia and bipolar disorder there are some evidence suggesting
that schizophrenia may be genetically related to mood disorders
with regard to psychotic symptoms (continuum model of psychosis).
In consensus with this model, we have previously reported an inbred
multigeneration family overloaded with distinct psychotic disorders
(schizophrenia, schizoaffective, bipolar and unipolar disorders with
psychotic features) in 18 affected members of the pedigree (Prog.
Neuro-Psychopharmacology and Biological Psychiatry, 2004, 28; 255-
266). Chromosome 8p12 region containing neurogulin 1 (NRG1) gene
was excluded by both linkage and haplotype analysis for this particular
family. A total of 134 parent-offspring trios with psychotic disorders (53
schizophrenia; 5 schizoaffective; 70 bipolar affective disorders with
psychosis and 6 unspecified psychosis) were further genotyped with
the polymorphic DNA marker, D8S1810 located in the core at-risk haplotype
of the NRG1 gene. There was no evidence for overtransmission
of a spesific allele of the DNA marker D8S1810 to affected offspring
using broad model including distict types of psychotic disorders
. We have observed an overtransmission for 206 bp allele (allele 6)
of D8S1810 to affected offspring when we used a narrower (schizophrenia
and schizoaffective disorder only) model in the TDT analysis
( p= 0.0081 after correction p= 0.07). These preliminary results do not
support the hypothesis that NRG1 also plays a role in influencing distict
types of psychotic disorders. (Supported by Hacettepe University
Research Foundation: 06 01 101 020; NARSAD: 2003II)
P1051. The MLPA-dHPLC approach of the NF1 gene analysis: a
french experience
S. Pinson 1,2 , C. Vallet 1 , S. Lefebvre 1 , P. Combemale 3 , B. Chambe 1 , A. Toussaint
1 , S. Giraud 1 , C. Bellané-Chantelot 4 , D. Vidaud 4 , C. De Toma 5 , P. Wolkenstein
4 , A. Calender 1 ;
1 Hospices Civils de Lyon, Lyon, France, 2 NF France, Lyon, France, 3 HIA Desgenettes,
Lyon, France, 4 Assistance Publique de Paris, Paris, France, 5 Centre
Du Polymorphisme Humain, Paris, France.
The identification of mutations in the NF1 gene causing type 1 neurofibromatosis
(NF1) is still presenting a considerable amount of work
mainly because of the large size of the gene (350 kb - 60 exons) and
the restricted number of recurent mutations. The high frequency of
NF1 which is affecting 1 in 3500 individuals made us choose two complementary
methods to perform NF1 gene analysis:
- the multiplex ligation-dependant probe amplification (MLPA) for the
large deletion and duplication detection (P081-P082)
2