2008 Barcelona - European Society of Human Genetics

Clinical genetics
consistent finding in Cockayne Syndrome,fibroblasts,marked sensitivity
to UV radiation,deficient recovery or RNA syntesis following UV
damage(and impaired repair of) activity transcribed genes,or transcription
couple repair .
PND of CS has been reported by analysis of UV light sensitivity and
DNA repair in fetal cells obtained by CV or Amniocentesis .
P01.262
complete androgen insensitivity syndrome within a large
turkish family from southeast of Anatolia
G. Cankus 1 , G. Ogur 2 , E. Ozturk 3 , C. Kilicarslan 1 , O. Balat 3 , S. Pehlivan 1 ;
1 Gaziantep University, Faculty of Medicine, Department of Medical Biology,
Gaziantep, Turkey, 2 Ondokuz Mayis University, Faculty of Medicine, Department
of Medical Genetics, Gaziantep, Turkey, 3 Gaziantep University, Faculty of
Medicine, Department of Gynecology and Obstetrics, Gaziantep, Turkey.
Complete androgen insensitivity syndrome (CAIS) due to inactivating
mutations of the androgen receptor (AR) is an androgen receptor function
disorder . Here, we present a large family with 6 children out of
which 4 was CAIS affected . Cytogenetic analysis of the two healthy
sibs revealed one brother (46,XY), one sister (46,XX) and four affected
sisters with a normal male karyotype: 46,XY . The mother, the father and
5 sisters were tested with STR markers from X and Y chromosomes to
evaluate the origin of X chromosomes in affected versus non-affected
siblings . AMEL, XE1 (DXS6803), XE3(DXS6809), XHPRT(DXS6854),
X22 (DXS8377) markers were used for the X chromosome and SRY,
AMEL, YE4 markers were used for the Y chromosome . In all affected
CAIS sisters, an X pattern similar to one of the two X chromosomes
from the mother was observed and the Y markers correlated well with
the father’s Y markers as expected . The unaffected sister did not possess
the relevant X haplotype; thus, she was presumed not to be
a carrier . Lately this unaffected girl is reported to have two healthy
daughters .
Key words: Complete androgen insensitivity syndrome, large family,
STR markers, PCR .
P01.263
Evaluation and management of patients with complex
chromosomal abnormalities
C. Rusu, M. Gramescu, V. Gorduza, A. Sireteanu, I. Ivanov, M. Covic;
University of Medicine, Iasi, Romania.
We present 5 cases, apparently simple, but with complex chromosomal
abnormalities on the karyotype, in order to discuss the importance
of the cytogenetic evaluation for the management of the case and the
genetic counselling offered to the family .
Case 1: male, 7 years old, first child of an apparently healthy, young,
unrelated couple, who had also a miscarriage . The mother was pregnant
again . Physical examination: typical aspect of Down syndrome .
Karyotype: 46,XY,-13,+rob(13;21)/47,XXY,-13,+rob(13,21) . Mother:
carrier of the robertsonian translocation, as well as the fetus .
Case 2: male, 6 month old, third child of an young, unrelated couple .
The mother has been diagnosed with syphilis during the pregnancy .
Physical examination: mild aspect of Down syndrome . Karyotype:47
,XY,t(1;2)(p32-pter;q37-qter),-3,-21,+der(3)rcp(3;21)(p11 .1;q22 .2),+de
r(21)rcp(3;21)(p11 .1;q22 .2),+21 . Parents: normal karyotype .
Case 3: female, 7 years old, first child of an apparently healthy, young,
unrelated couple, that has also a healthy son . Physical examination:
mild aspect of Turner syndrome . Karyotype: 44,X,der(13;14) . Father:
carrier of the robertsonian translocation .
Case 4: male, 5 years old, first child of an apparently healthy, young,
unrelated couple, that has also a healthy son . Physical examination:
typical aspect of trisomy 8 . Karyotype: 47,XY,+8/47,XY,+8q/46,XY/
45,X . Parents: normal karyotype .
Case 5: female, evaluated duet o fertility problems . Karyotype:
45,X,inv9/47,XXX,inv9 .
The mechanism that led to the complex chromosomal abnormality, as
well as the clinical picture, the management and genetic counselling
are discussed for all cases .
In conclusion, we present 5 cases of complex chromosomal rearrangements
to illustrate particular situations (apparently simple cases, but
with complex karyotype) and to discuss genetic counselling in these
situations .
P01.264
importance of early track down of congenital cardiac
malformations
D. Iacob 1 , M. Boia 1 , R. E. Iacob 2 , A. Manea 1 , M. Dima 1 ;
1 University of Medicine and Pharmacy Timisoara, Romania, Timisoara, Romania,
2 Clinical emergency Hospital Arad - Pediatric Surgery and Orthopedics
Department, Arad, Romania.
Introduction: Congenital malformations are the main cause of death in
the first year of life; therefore, early identification of etiology and right
therapeutic decision are vital problems in pediatric services .
Objectives: genetic consult and family investigation; examination, investigation
and selection of cases which require special methods of
diagnosis, interdisciplinary consult, adaptation of European pattern for
the anomalies management .
Material and method: The study includes 187 children with age of
0-1 year, consulted, hospitalized and investigated in Premature and
Neonatology Department of Clinical Emergency Hospital for Children
‘L . Turcanu’ Timisoara between 2001 and 2006 . Case distribution by
etiology shows a clear prevalence of genetic determination: chromosomal
45 cases (24%), monogenic 17 cases (9%), and polygenic 86
cases (46%), in comparison with epigenetic etiology 39 cases (21%) .
The study of chromosomal anomalies case distribution with cardiac
involvement shows an increased frequency of Down syndrome cases
and cardiac disorders (50%) . Cardiac pathology associated to some
monogenic syndromes is obvious in Holt-Oram syndrome, Marfan syndrome,
Bourneville tuberoses sclerosis, Hurler syndrome and Carpenter
syndrome; the distribution is similar to the one reported in similar
studies and correlated with the incidence of these diseases in general
population .
Conclusion: Congenital cardiac diseases represent pathology difficult
to quantify .
These patients and their families are confronted with dramatic situations
because of diagnosis delay, absence of therapeutic response
and, mostly, of lack of sanitary and social support .
P01.265
Preventive effect of periconceptional folic acid supplementation
on the risk of congenital heart defects: A registry based casecontrol
study in the Netherlands
H. E. K. De Walle;
Eurocat registration Northern Netherlands, Groningen, The Netherlands.
Evidence is emerging that multivitamins containing periconceptional
folic acid supplementation protects against the occurrence of congenital
heart defects (CHD) . Postulating that folic acid is responsible for the
reduction in CHD risk we used data from a large surveillance for birth
defects (EUROCAT- Northern Netherlands registry from 1981 to 2006)
to perform a case-control study to investigate the effect of periconceptional
folic acid supplementation on CHD risk .
The cases consisted of mothers who delivered infants with isolated
or complex heart defects, without any syndrome or genetic abnormality
(N=613, years 1996-2005) .The control group consisted of mothers
who gave birth to children with a known chromosomal or genetic defect
or infants with other congenital malformations (N=2385) . In both
the case and control group, mothers of children with oral cleft, urinary
tract, limb reduction and neural tube defects were excluded, because
the risk of these defects are probably reduced by maternal folic acid
supplementation . Potential confounding factors of periconceptional folic
acid use included; maternal body mass index, education, maternal
age at delivery of index baby, smoking behaviour and alcohol use during
pregnancy were explored .
Adequate use of periconceptional folic acid supplements revealed an
odds ratio of 0 .81 (95%CI 0 .67-0 .96) for all types of CHD . Subgroup
analysis showed an odds ratio of 0 .60 (95%CI 0 .42-0 .86) for isolated
ventricular septal defects . Periconceptional folic acid supplements appear
to reduce the prevalence of CHD with approximately 20% . Considering
the relatively high prevalence of CHD worldwide the findings
of this study are important for public health .