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

Clinical genetics
In third case : mutation G8494 A in ATP-ase gene and C11674T in ND
4 gene . In fourd case G 8573A mutation of ATP -ase 6 region.In addition
were found two nonsense bases changes .The PCR method for
sequence of mt DNA open new possibility for optimize the diagnosis
and treatment of these patients in Clinical genetics.
P0028. Partial duplications of the ATRX-gene cause the ATR-X
syndrome
B. Thienpont 1 , T. de Ravel 1 , H. Van Esch 1 , D. Van Schoubroeck 2 , P. Moerman 3 ,
J. R. Vermeesch 1 , J. Fryns 1 , G. Froyen 4 , C. Badens 5 , K. Devriendt 1 ;
1 Center for Human Genetics, Leuven, Belgium, 2 Department of Obstetrics, Leuven,
Belgium, 3 Department of Pathology, Leuven, Belgium, 4 Human Genome
Laboratory, Center for Human Genetics, Flanders Interuniversity Institute for
Biotechnology, Leuven, Belgium, 5 Centre d’Enseignement et de Recherche en
Génétique Médicale, Faculté de médecine, Marseille, France.
ATR-X syndrome is a rare X-linked disorder characterized by profound
mental retardation, a characteristic face, skeletal abnormalities and
alpha thalassaemia. We show that some of the patients suspected of
having ATR-X carry do not carry small mutations at the single bp level,
but instead carry intragenic duplications in the ATRX gene, further expanding
the spectrum of mutations found in ATRX. We identified such
a duplication in two families.
In the absence of an etiological diagnosis, array CGH analysis was
performed on two siblings. This showed they carry a complex chromosomal
aberration: an intragenic duplication in ATRX and an additional
duplication upstream of this gene. We show that these duplications
lead to an absence of ATRX mRNA and of the protein.
We next extended this observation to a group of 50 patients suspected
of having ATR-X but without a detected sequence alteration. Quantitative
PCR screening identified one additional patient, carrying a small
intragenic duplication. These findings underscore the need for including
quantitative analyses to mutation analysis of the ATRX gene.
P0029. Interstitial duplication 15q11-13 in a patient with Asperger
autism and seizures
B. Oehl-Jaschkowitz 1 , T. Martin 1 , E. Goettert 1 , A. Christmann 1 , C. Freitag 2 ;
1 Praxis fuer Humangenetik, Homburg/Saar, Germany, 2 Klinik fuer Kinder -und
Jugendmedizin, Universitaet des Saarlandes Homburg/Saar, Germany.
We present a boy who was diagnosed to have Asperger autism at the
age of 19 years.
Furthermore the boy suffers from seizures since the age of 16 years.
Intelligence is in normal range.
The patient finished non-classical secondary school with good marks.
Afterwards he tried to
graduate from expert school for social sciences which could not be
completed because of his special defects in social competence and
communication skills, and his deficiency of empathy which, at the end
of the initiated diagnostic procedure, led to the diagnosis of Asperger
autism.
Since recent studies (1) were able to show a defined interstitial duplication
of chromosome15q11-13 in a few patients with autism disorder
(1-3%) we investigated this region with respect to this abnormality.
We were able to show a duplication of the region of interest with the
proof of three alleles for the internal markers D15S122, D15S822 and
D15S1234.
Furthermore we could confirm this result with FISH using the probe
GABRB3 (15q11-12),which showed three signals on meta- and interphase
chromosomes.
Parental investigations (FISH and molecular analysis) were inconspicuous.
Microsatellite-analysis showed that the duplication did arise from
the boy`s maternal chromosome 15, as described in the literature (2).
The proposed mechanism is misalignment in maternal meiotic recombination.
The influence of parental imprinting on phenotype will be discussed; the
variation of the symptoms of the yet published cases will be shown.
P0030. An autosomal dominant loose anagen hair syndrome:
Clinical and genetic analysis
S. Ari 1 , U. Ratnamala 1 , U. C. Patel 2 , J. V. Solanki 3 , D. G. Saple 4 , S. K. Nath 5 , U.
Radhakrishna 1 ;
1 Green Cross Blood Bank & Genetic Research Centre, Paldi, Ahmedabad,
India, 2 Departments of Animal Genetics and Breeding, Veterinary College,
Gujarat Agriculture University, Anand, India, 3 Departments of Animal Genetics
and Breeding, Veterinary College, Gujarat Agriculture, University, Anand, India,
4 Department of Dermatovenereology & AIDS Medicine, G.T. Hospital, Grant
Medical College, University of Mumbai, Mumbai, India, 5 Arthritis and Immunology
Research Program, Oklahoma Medical Research Foundation, Oklahoma
City, OK, United States.
Loose anagen hair syndrome (LAHS: OMIM 600628) is a non-inflammatory
hereditary hair disorder characterized by anagen hairs of
abnormal morphology that are easily and painlessly pluckable from
the scalp. The hair is usually sparse, thin, slow growing and naturally
does not grow beyond the nape of the neck. The phenotype has been
recently described and its prevalence is yet to be defined. It affects
both the genders equally. The condition is usually isolated; however
few cases associated with other genetic conditions are also reported.
There are several isolated cases and families reported with LAHS.
We have studied one large Indian LAHS pedigree, with an autosomal
dominant mode of inheritance, containing 63 individuals including
22 affecteds (12 males and 10 females). The phenotype appears
to be100% penetrance in this family since no skipping of generation
was observed. All affected had typical characters of loose anagen hair
syndrome. The expression of the phenotype was an early age of onset.
A hair pull test of all affected individuals extracted multiple hairs
easily and painless and there were no sign of scalp inflammation or
scarring. Light microscopic examination was also consistent with LAS.
Majority of the affected members including all females never cut their
hair, however three males has the history of seldom cutting their hair.
Nine patients had an additional clinical phenotype of partial woolly hair
and five females had fair hair color. There were no other associated
anomalies observed in this family. Cytogenetic analysis of four affected
individuals did not show any abnormality. We are planning to perform a
high-density genome-wide linkage analysis to identify the responsible
LAHS susceptibility locus. Email: madam_fille@yahoo.com
P0031. Genetic abnormalities in patients with azoospermia in
ART programs
N. V. Zotova, E. V. Markova, N. V. Kazmina, O. A. Serebrennikova, T. A. Zaitseva,
A. V. Svetlakov;
Center for Reproductive Medicine, Krasnoyarsk, Russian Federation.
Azoospermia is the most severe form of male infertility. Thanks to
developing of assisted reproductive techniques (ART) many patients
come to reproductive centers for infertility treatment. Azoospermia may
be caused by number of genetic abnormalities. In this study we investigated
molecular and cytogenetic defects in 57 azoospermia patients
(age 31.6±0.7). Azoospermia was defined as the total absence of spermatozoa
in ejaculate even after it centrifugation. DNA was extracted
from peripheral blood. We analyzed 12 mutations of CFTR gene and
11 STS involving the AZFa, AZFb and AZFc regions using PCR and
PCR/RELP. The karyotype analyses were performed by GTG-banding
technique for at least 12 metaphases of standard lymphocyte culture.
In all cases of mosaic forms in karyotype FISH technique was used for
1000 cells. Y chromosome microdeletions were found in six cases of
azoospermia men (10.5%): three with AZFc, one with AZFb, and two
with both AZFc and AZFb. Mutations of CFTR gene (only F508del/-
) were revealed in 4.4%. Chromosome abnormalities were observed
in 21.6% cases, including 47,XXY karyotype in six cases (three of
them were mosaic variants). One patient had an XX male syndrome,
with presence of SRY gene. Two patients had combined defects: one
with cytogenetically detected deletion of Y chromosome and AZFb/
c microdeletion, and one with both AZFb microdeletion and mosaic
Klinefelter`s syndrome. Thus, genetic abnormalities were determined
in 32% of azoospermia cases. Genetic testing is necessary to determine
aetiology of azoospermia and to choose ART strategies between
ICSI with testicular spermatozoa, PGD, or sperm donation.
P0032. Barth syndrome associated with compound hemizygosity
and heterozygosity of the TAZ and LDB genes
A. Brega 1,2 , N. Marziliano 3 , S. Mannarino 4 , L. Nespoli 5 , M. Diegoli 6 , M. Pasotti 6 ,
C. Malattia 5 , M. Grasso 6 , A. Pilotto 6 , E. Porcu 6 , A. Raisaro 7 , C. Raineri 8 , R.
Dore 9 , P. P. Maggio 10 , E. Arbustini 6 ;
1 University, Milan, Italy, 2 Department of Biology and Genetics for Medical Sciences,
Milan, Italy, 3 Centre for inherited cardiovasculat diseases, Foundation
IRCCS Policlinico San Matteo, Pavia, Italy, 4 Pediatric Cardiology, Foundation
IRCCS Policlinico San Matteo, Pavia, Italy, 5 Pediatric cardiology, Foundation
IRCCS Policlinico San Matteo, Pavia, Italy, 6 Centre for inherited cardiovascular
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