2008 Barcelona - European Society of Human Genetics

Cancer genetics
a 46,XY karyotype .
Conclusion: Biochemical analysis of the amniotic fluid through 7DHC
levels is a rapid and efficient prenatal diagnosis test for SLOS and is
family relieving before a results of molecular analysis is achieved . Both
pre- and post-natally, association of cleft palate, ambiguous genitalia
and oligodactyly in a patient should promt the physician to evaluate
SLOS .
P03.77
Partial monosomy of chromosome 8p and partial trisomy
of chromosome 7p associated with a Fryns syndrome-like
phenotype: Prenatal diagnosis
C. Fourneau, S. Rombout, B. Grisart, C. Verellen-Dumoulin;
Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gossselies,
Belgium.
We wanted to insist on the importance of a good resolution chromosome
analysis for finding subtle chromosomal abnormalities in prenatal
diagnosis specially when there are abnormal ultrasound findings.
We report a prenatal diagnosis performed following the discovery at
ultrasound of a diaphragmatic hernia and a Dandy Walker malformation
at 16 weeks of pregnancy .
A descision was made to interrupted the pregnancy and the fetal autopsy
revealed signs of a Fryns syndrome that is thought to be inherited
in an autosomal recessive way : craniofacial dysmorphism (macrocephaly,
short webbed neck, coarse face, flat and broad nasal bridge,
anteverted nostrils, hypertelorism, microretrognathia, large mouth with
thin lips, low-set ears with posterior angulation), Dandy-Walker malformation,
diaphragmatic hernia, small penis with hypospadias .
Cytogenetic analysis on the amniotic fluid showed a partial monosomy
8p associated with a partial trisomy 7p which was initially interpreted
as a duplication 8p .
When the parents karyotypes were established, we discovered that
the father had a terminal reciprocal translocation between the short
arm of chromosome 8 and the short arm of chromosome 7 with karyotype
46,XY,t(7;8)(p21;p23) .
The fetus had thus inherited an unbalanced translocation with karyotype
46,XY,der(8)t(7;8)(p21;p23)pat .
Array CGH and FISH analysis are under way in order to characterize
the break points .
P04. Cancer genetics
P04.001
the APc gene mutations status in Polish FAP patients
A. Plawski 1 , M. Podralska 1 , D. Nowakowska 2 , T. Banasiewicz 3 , J. Paszkowski 3 ,
P. Krokowicz 3 , E. Czkwanianc 4 , W. Cichy 3 , J. Lubinski 5 , G. Kurzawski 5 , A. Dobrowolska-Zachwieja
3 , J. Steffen 2 , M. Drews 3 , R. Slomski 1 ;
1 Instytitute of Human Genetics, Poznan, Poland, 2 Institute of Oncology, Warszawa,
Poland, 3 Karol Marcinkowski University of Medical Sciences, Poznan,
Poland, 4 Institute of Polish Mother’s Memorial Hospital, Lodz, Poland, 5 Department
of Genetics and Pathology, Pomeranian Medical University, Szczecin,
Poland.
Familial adenomatous polyposis (FAP) is a genetically conditioned
predisposition to occurrence of numerous adenamatous polyps in colon
and rectum . The polyps arises in second decade of life and left
untreated develop to the tumor . Other extracolonic features may include
polyps in the upper parts of the gastroenterological tract, desmoid
tumours, ocular lesions, osteomas, dental abnormalities, and
malignancies in other organs . FAP incidence is estimated at 1/10,000 .
FAP arises due to germ line mutations in the adenomatous polyposis
coli (APC) gene, which was first described in 1991. The APC gene
mutations are studied at the Institute of Human Genetics in Poznan for
last 10 years . The Institute of Human Genetics in Poznan cooperates
with medical centers from all country, what permitted us to create the
DNA bank for Polish FAP patients . Till now samples from 340 families
were collected . Seven hundred DNA samples from Polish FAP families
were banked so far . The APC gene we screened for mutation in 300
probands. We identified 74 point mutations in 124 FAP families. The
detected mutation can be considered characteristic for Polish population
due to 34 types of them has not described in other population .
Among detected mutations seven occurred in two or to the greater
number of families . Occurrence of the APC gene large rearrangements
was studied in 95 families. We identified rearrangements in 24 fami-
lies in two cases it were deletion of whole APC gene . This work was
founded by the Ministry of Education and Science, Poland, grant number
2PO5A10728
P04.002
Frequent association of sporadic desmoid tumors with germline
APc mutations
T. A. Muzaffarova1 , O. V. Novikova2 , I. V. Droshneva2 , E. K. Ginter1 , A. V. Karpukhin1
;
1 2 Research Centre For Medical Genetics, Moskow, Russian Federation, Moscow
Herzen Oncology Institute, Moskow, Russian Federation.
As it is known somatic APC mutations are present in desmoid tumors .
However there is no information about the role of germline APC mutations
in patients with desmoid tumors and without history of familial
adenomatous polyposis (FAP) .
We examined 31 patients (17 female and 14 male) with apparently
sporadic desmoid tumors and without clinical features or family history
of FAP . Peripheral blood lymphocytes from these patients were investigated
for the APC gene mutations .
Germline APC mutations were found for 6 of 31 the patients (19%) .
Four mutations - 1462del5, 1465delAG, 1525insT and R2505Q were
found for the first time. The mutation 1465delAG was seen twice. The
mutations were located predominantly between 1450 and 1525 codons
of the APC gene (4 of 5 mutations) .
The age of desmoid diagnosis among patients with the APC mutations
was ranged from 1 month to 23 years .Colonoscopy was performed
for two patients with germline APC mutations and highest age . There
were no polyps in colon of 25 years old female . Another patient, 19
years old female had gastric polyps and no colon polyps . In our sample
there were six patients with multiple desmoids tumors and five of them
were found with germline APC mutations . One patient with APC mutation
had intraabdominal desmoid at age 4 year.Thus for the first time
it is shown association of sporadic desmoid tumors with APC germline
mutations . The patients with germline APC mutations are characterized
by early disease onset and severe desmoid phenotype .
P04.003
molecular Analysis of the APC gene in Families Affected by FAP:
2 Novel mutations
M. Noruzinia 1 , N. Vasli 2 ;
1 Tarbiat Modares University, Tehran, Islamic Republic of Iran, 2 Department of
genetics, School of Sciences, Azad Olum Tahghighat University, Tehran, Iran,
Tehran, Islamic Republic of Iran.
Introduction: Familial adenomatous polyposis (FAP) is an autosomal
dominantly inherited susceptibility to colon cancer with high penetrance,
characterized by more than 100 adenomatous polyps in the
colon and rectum . Additional features may include desmoids tumors,
polyps in the upper gastrointestinal tract, osteomas and congenital
hypertrophy of the retinal pigment epithelium (CHRPE) . APC (Adenomatous
Polyposis Coli) gene is mutated in most of these carriers . Presymptomatic
genetic diagnosis in this syndrome is obligatory as near
100% of carriers of deleterious mutations will present colon cancer by
40 years . The APC gene has 15 exons and an ORF with 8538 nucleotides
which code a protein with 2843 amino acids .
Materials & Methods: CSGE on APC was set up and used as screening
method to analyze APC alterations . Direct sequencing was used to
confirm the presence of mutation or polymorphism.
Results: we found deleterious mutations in all patients . Two novel mutations
c .3921_3925del AAAAG in MCR and c .1862C>G in exon 14 of
APC were found in 2 families with classical FAP
Conclusion: Conformation Sensitive Gel Electrophoresis can be used
as a simple, cost-effective and sensitive mutation screening test in
complex genes where sequencing as the gold standard of mutation
detection techniques is expensive to use in the first line.
P04.004
15 years of familial adenomatous polyposis diagnostics in the
czech Republic
K. Veselá, J. Štekrová, M. Florianová, K. Zídková, J. Kotlas, M. Kohoutová;
Institute of Biology and Medical Genetics of the 1st Faculty of Medicine Charles
University and General Teaching Hospital, Prague, Czech Republic.
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome
with almost 100 % risk of colorectal cancer . FAP exists in two