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

Cytogenetics
140A:1655-1657 (2006)]. Since responsible genes for the OCTS have
not been isolated, though it is thought to be a heterogeneous condition,
it would be important to investigate the precise structure for the
breakpoints.
Fluorescence in situ hybridization (FISH) analysis identified a breakpoint
spanning BAC clones on the chromosome 3q containing a gene
encoding a member of the immunoglobulin superfamily (IgSF). Following
FISH analysis by cosmids subcloned from the BAC clone plus
Southern blot analysis demonstrated the breakpoint was in the gene.
Inverse PCR and sequencing revealed the breakpoint was in exon 5
of the gene. Sequence analysis for the other breakpoint at 18q12.1
indicated that the translocation was occurred with 10-bp deletion in the
exon 5. We could not find any genes around the other breakpoint according
to the Genome Browser web site. Semi-quantitative RT-PCR
analysis showed that the IgSF gene expression in B cells of the patient
was reduced approximately 50% of the normal level.
P0414. Translocation (2;5) (p21-p15): Clinical findigs in a female
case
G. Hernandez-Zaragoza 1 , V. C. Ledezma-Rodriguez 1 , L. M. Aguirre-Salas 2 , M.
Maya-Castillo 3 , R. E´Vega-Hernandez 1 , I. J. Garcia-Gonzalez 1 , V. M. Anguiano-
Alvarez 1 , M. P. Casillas-Avila 1 , J. Armendariz-Borunda 4 , N. O. Davalos 5 ;
1 Instituto de Genetica Humana, Guadalajara, Jalisco, Mexico, 2 HRVGF,
ISSSTE. Departamento Endocrino-Pediatria, Zapopan, Jalisco, Mexico, 3 Teleton,
Guanajuato, Mexico, 4 Departamento de Biologia Molecular y Genomica,
CUCS, U de G., Guadalajara, Jalisco, Mexico, 5 Instituto de Genetica Humana,
CUCS, U de G. HRVGF, ISSSTE. Departamento de Genetica, Guadalajara,
Jalisco, Mexico.
INTRODUCTION: The concurrence of this translocation involving a
t(2;5) (p21-p15) has not been previously reported. We report a female
case with this translocation.
CASE REPORT: The propositus a 5 years-old female, was the product
of the second pregnancy from non-consanguineous parents. The
mother presents an obstetric history of gravida: 2, abortion 1, caesarean
1. The pregnancy was interrupted by caesarea at 7 months of gestation
by a premature rupture of membranes. At birth the weight was
2 kg, and multiple dysmorphic features were characterized by marked
hypotonia, developmental delay and poor growth. She presented pyloric
hypertrophic confirmed by barium studies. Surgical repair was
performed at 4 months old without complications. The physical examination
at this time showed height 15,500 gr (10-20 centile) weight
96.5 cm (3rd centile) and OFC 48 cm (10-20centile). Facial dismorfism
characterized by strait biparietal diameter, prominent metopic suture,
sparse eyebrows, hipertelorism, internal epicanthal folds, downslating
palpebral fissures, high nasal bridge, broad nose, downturned corners
of the mouth, thin superior lip and high palate; in hands: clinodactyly
and camptodactyly of 5th fingers bilateraly was observed.
Hipoacusia was diagnosed by audimetry and craneal CT shown cochlear
bilateral agenesia. Laboratory studies were normal. Standard
chromosome studies on blood with 550-banded resolution revealed a
karyotype of 46,XX, t(2;5)(p21-p15).
DISCUSSION: Few chromosomal translocation that involve chromosome
2 and 5 were reported, but all are related with other breakpoints
(Kimberley 1999, Gilliam 2000). The molecular cytogenetic studies
should be made in the patient to identify the genes involve in the translocation
breakpoints.
P0415. Chromosomal Rearrangements in Patients with
Reproductive Problem
S. Midyan, L. Nazaryan, G. Shakhsuvaryan, L. Khachatryan, T. Sarkisyan;
Center of Medical Genetics and Primary Health Care, Yerevan, Armenia.
Pregnancy loss, particularly early miscarriage is a common problem
that affects many women and their partners. Most spontaneous miscarriages
are caused by an abnormal karyotype of the embryo. Balanced
reciprocal translocations are present in 2-5% of couples who
experience recurrent pregnancy loss. Structural chromosome rearrangements
may result in unbalanced chromosome errors in pregnancies.
We carried out cytogenetic investigations in 262 couples referred
for recurrent spontaneous abortions (RSA). Chromosome analysis
was performed on peripheral blood lymphocytes and GTG banding
analyses at 550-600 band level. FISH technique was applied using
WCP probes for 1 and 2 chromosomes.
We identified six cases of reciprocal translocations. Robertsonian
12
translocations were detected in six cases (all carriers were female|)
and pericentric inversion was found in one case. Sex chromosome
abnormality was defined in one case with mosaic Turner syndrome.
All cases of structural chromosome abnormalities caused the miscarriages,
except one where a child with different clinical manifestation
was born. As result of unbalanced gamete formation the translocation
46,XYt(4;9)(q26;p23) lead to partial trisomy of 4q26 region.
In our study the overall frequency of balanced chromosomal rearrangement
as the main group of chromosomal aberrations was found
to be 3,1%.
In conclusion we insist on the advantage of systematically performing
a karyotype in case of RSA consisting on the detection of chromosomal
abnormalities. The central concept in genetic counseling is the
estimation of the probability of unbalanced progeny at birth and other
unfavorable pregnancy outcomes as well the prognosis of success of
assisted reproductive technologies.
P0416. Two cases of unbalanced offspring due to rare adjacent-2
segragation in non-relative translocation 4;15 carriers
R. Mihalova 1 , K. Vesela 1 , A. Baxova 1 , M. Zapadlo 2 , B. Zlatohlavkova 2 ;
1 Institute of Biology and Medical Genetics, 1st Faculty of Medicine of Charles
University and General Teaching Hospital, Prague, Czech Republic, 2 Department
of Gynaecology and Obstetrics, 1st Faculty of Medicine of Charles University
and General Teaching Hospital, Prague, Czech Republic.
We report on two patients with partial trisomy of chromosome 4 and
partial monosomy of chromosome 15 resulting from parental translocation
4;15. Translocation carriers were non-relative, other unbalanced
offspring in these families have not been described although miscarriages
and stillbirths have as well as liveborns been reported in family
histories of both carriers. Further investigation with FISH has revealed
different breakpoints on chromosome 15, proximal from Prader-Willi/
Angelman specific region and distal, respectively. Obvious phenotypic
difference was probably due to 15q11-13 loss of one of our patients.
Because of different segregation during meiosis I, various unbalanced
karyotypes can arise in balanced translocation carriers. The frequency
of unbalanced gametes varies from one translocation to another. Adjacent-2
segregation mode, in which each daughter cell gets chromosomes
with homologous centromeres, is quite rare - on an average
5-10%. The type of unbalanced segregation depends on the nature
of the chromosome involved and the breakpoints. Considering the
pachytene diagram determined by breakpoints, the balanced translocation
t(4;15)(q21;q11.2) and t(4;15)(q21;q13.1), respectively seems
predisposed to chromosome imbalance through adjacent-2 segregation.
Genetic counseling focused on prediction of the mode of imbalanced
segregation will be discused.
P0417. Identification of a novel deletion in 3q23-25 in Treacher
Collins Syndrome
M. Kumar 1 , R. Kumar 2 , M. Tanwar 2 , R. Dada 2 , S. Ghose 3 , J. Kaur 1 ;
1 Ocular Biochemistry, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All
India Institute of Medical Sciences, New Delhi, India, 2 Department of Anatomy,
All India Institute of Medical Sciences, New Delhi, India, 3 Dr Rajendra Prasad
Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New
Delhi, India.
Treacher Collins syndrome (TCS) is a rare genetic disorder characterized
by craniofacial deformities. TCS occurs in an approximate rate of
1:50,000 of live births. The disorder is inherited in an autosomal-dominant
pattern. The typical clinical features include downward slanting
eyes, sparse eyelash, micrognathia, cleft palate, microtia and notch in
the lower eyelid called coloboma. More than 129 different mutations
have been reported in patients with TCS. Patients with TCS were reported
to be heterozygous for mutations in the TCOF1 gene, which is
located in 5q32-q33.1. This gene codes for a protein of at least 1411
amino acids, treacle, which is a nucleolar phosphoprotein. The protein
coded by this gene assists in protein sorting during particular stages in
embryonic development, particularly that of the structures of the facial
bones. There are reports with a small interstitial deletion of 3p,46,XY,
del(3)(p23p24.12) and pericentric inversion inv(2) (p11.2q21) associated
with TCS. We have done the cytogenetic analysis of a family with
typical physical features of TCS. The high-resolution G-banding analysis
has shown a small novel deletion in 3q23-25. This novel deletion in
3q23-25 has been found in two members of the family. Linkage of TCS
to the 5q31.3q33.3 region has been established. We also confirm a de-