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

Clinical genetics
syndrome is a very heterogeneous condition and the patients should
be followed for future development of clinical criteria.
P0129. Psychological manifestations in Romanian haemophilics
M. Mihailov, M. Serban, S. Arghirescu, M. Puiu;
University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania.
Introduction. Haemophiliacs often have to adjust their aspirations, lifestyle
and employment options. In Romania and in other developing
countries, lack of adequate therapy generates fear and uncertainty.
Patients with high complications rate may develop psychological disorders.
Aim of the study was to evaluate frequency and type of psychological
manifestations in haemophiliacs.
Material and method. Our study group consisted of 234 haemophiliacs
registered and treated in Haemophilia Center Timisoara. We analyzed
psychological complications according to haemophilia severity and patients’
age.
Results. In our patients, psychological complications appeared in
16.24% of cases. 31.58% of patients with psychological complications
presented associated psychological manifestations. In 4.27% of haemophiliacs
with psychological manifestations neuro-sensitive-sensorial
complications were noticed.
The majority of patients with psychological complications (81.6%) had
severe haemophilia. High frequency of haemartrosis in these patients,
frequent and long hospitalizations, high chronic arthropathy rate which
produces disability and affects body image are important factors of psychological
manifestations appearance. Most patients with psychological
complications (76.3%) were from other counties, major deficiencies
in haemophilia care representing a permanent distress. Mean age of
patients with mental complications at diagnose was 14.2 (SD=9.840.
Opioid abuse (12 cases) was the main complication and was signalized
only in adults, the explanation being that in this age group, most
of the patients present severe chronic haemophilic arthropathy, which
causes chronic pain and disability.
Discussions and conclusions. Despite all difficulties, it is essential
to diagnose and treat psychological complications in haemophiliacs,
presence of a psychologist in the multidisciplinary haemophilia care
team being indispensable.
P0130. Role of mtDNA in Iranian patients with Hypertrophic
Cardiomyopathy
M. Montazeri 1 , E. V. Zaklyazminskaya 2 , M. Houshmand 1 , M. Peyghambari 3 , G.
Estahbanati 3 ;
1 NRCGEB, Tehran, Islamic Republic of Iran, 2 RussianResearch Center of Medical
Genetics, Laboratory of DNA Research, Moscow, Russia, Moscow, Russian
Federation, 3 2Iran University of Medical Sciences, Shaheed Rajaei Cardiovascular
Medical Center, Tehran, Iran, Tehran, Islamic Republic of Iran.
Hypertrophic cardiomyopathy (HCM) is characterized by hypertrophy
of ventricles and intrventricular septum. Patients could develop serious
complications including heart failure, arrhythmias and sudden death.
Recently mitochondrial DNA mutations have been associated with cardiomyopathies.
Mitochondria are the major site of energy production
in the cell. Thus, it is reasonable to assume that energy dependant
tissues such as heart, affected by mitochondrial dysfunction. Mitochondrial
(mt) DNA mutations are hypothesized to be involved in the
pathogenesis of HCM. In this study, 31 Iranian HCM patients were
screened for mitochondrial DNA point mutations and deletions. Our
result showed three patients (5.76%) with a 7.4 kb deletion and one
patient (1.92%) with 4977 bp “common deletion. Mutations in G3338A
(Val>Met), G9053A (Ser>Asn), G9055A (Ala>Thr) and T3285C in
tRNA Leucine were found. We detected 41 polymorphisms in mtDNA
that 15 polymorphisms of them have not been reported before. Our
results suggest that an increased level of mitochondrial mutations may
be an indicator of DNA instability. Furthermore, mtDNA mutations may
play an important role in pathogenesis of cardiac arrest which has remained
unexplained for long. We are investigating pathogenesis these
findings
P0131. Screening of TMC1 gene mutations in DFNB7(11) locus
in autosomal recessive non- syndromic hearing loss Iranian
population.
N. Bazazzadegan 1 , N. Meyer 2 , K. Kahrizi 1 , M. Mohseni 1 , P. Imani 1 , N. Nikzat 1 ,
S. Arzhangi 1 , M. Seifati 1 , K. Jalalvand 1 , J. Malbin 1 , K. Javan 1 , M. Farhadi 3 , R. J.
H. Smith 2 , H. Najmabadi 1 ;
1 Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences,
Tehran, Islamic Republic of Iran, 2 Molecular Otolaryngology Research
Laboratories, Department of Otolaryngology Head and Neck Surgery, University
of Iowa, Iowa, IA, United States, 3 Research Centre of Ear, Nose, Throat, and
Head and Neck Surgery, Iran university of Medical sciences, Tehran, Islamic
Republic of Iran.
Mutations in the transmembrane channel-like gene 1 (TMC1) cause
prelingual autosomal recessive (DFNB7/11) and postlingual progressive
autosomal dominant (DFNA36) nonsyndromic hearing loss suggesting
that this protein plays an important role in the inner ear. These
loci map to the same interval on 9q13-q21. The TMC1 protein is predicted
to contain 6 transmembrane domains and to have cytoplasmic
orientation of N and C termini. Mutations in this gene have been reported
in North America in a family with autosomal dominant inheritance,
Sudan, also in our two neighbor countries Pakistan and Turkey.
Therefore we decided to study this locus in our population.
Thirty nine families with autosomal recessive and one family with autosomal
dominant non-syndromic hearing loss that include two or more
affected children were screened for DFNB7(11) locus by linkage analysis.
These families originated from different ethnic groups of Iranian
population and were negative for GJB2 and GJB6 mutations in locus
DFNB1 . We used D9S301, D9S175, D9S1876 and D9S1837 STR
(short Tandem Repeat) markers for this study.
Three out of forty families were linked to this locus. Mutation screening
of TMC1 gene in these families revealed a homozygous framshift
mutation (P.N150kfrx26) in one of the recessive families and a heterozygous
mutation (G417R) in dominant family. Mutation detection for
the other recessive family is undergoing.
We concluded that after DFNB1 and DFNB21 mutations, TMC1 gene
mutations are responsible for the most prevalent cause of non- syndromic
hearing loss in Iranian population.
P0132. Screening for 15 loci in the Iranian patients with
autosomal recessive non-syndromic hearing loss
H. Najmabadi 1 , C. Nishimura 2 , K. Kahrizi 1 , N. Bazazzadegan 1 , M. Mohseni 1 ,
Y. Riazalhoseini 1 , G. Asaadi Tehrani 1 , A. Daneshi 3 , M. Farhadi 3 , S. Yahyavi 3 , E.
Taherzadeh 1 , P. Imani 1 , R. Vazifehmand 1 , A. Anousheh 1 , A. Nazeri 1 , S. Abedini 1 ,
N. Nikzat 1 , S. Arzhangi 1 , R. J. H. Smith 2 ;
1 Genetics Research Center, The Social Welfare and Rehabilitation Sciences
University, Tehran, Islamic Republic of Iran, 2 Molecular Otolaryngology Research
Laboratories, Department of Otolaryngology, University of Iowa, Iowa,
IA, United States, 3 Research Center of Ear, Nose, Throat, and Head and Neck
Surgery, Iran university of Medical sciences, Tehran, Islamic Republic of Iran.
Autosomal recessive non-syndromic hearing loss is the most common
form of severe inherited hearing impairment. Mutations in GJB2 gene
have been reported to be the most common cause of ARNSHL in the
Northern European populations. These mutations are followed closely
by GJB6 deletion. Our previous studies showed that GJB2 mutations
and the GJB6 deletion do not play a significant role in the etiology of
deafness in Iran. In this study, we assessed the contributions made by
other loci to the ARNSHL genetic load in Iran. We have been screening
50 families with normal GJB2 and GJB6 alleles for DFNB1, DFNB2,
DFNB3, DFNB4, DFNB9 , DFNB21 and DFNB40 by linkage analysis
using, 3 STR markers for each locus. Some of the families have
been localized to above- mentioned loci. Then with exclusion of linked
families, the rest of families were screened for DFNB6, DFNB7(11),
DFNB8 (10) , DFNB12, DFNB16, DFNB18 , DFNB23 and DFNB29
loci. Seventeen families showed linkage to some of these loci. Three
families have been localized to DFNB4 with G334V, R409H and T420I/
1197DelT mutations in SLC26A4 gene , two families to DFNB21 with a
9611 bp deletion in exon 10 and 266 delT mutation in TECTA gene and
one family to DFNB7(11) with P.N150kfrx26 mutation in TMC1 gene.
Mutation screening of SLC26A4, MYOVIIA, TMPRS53, MYO15A,
Harmonin and TMC1 genes for other 11 families is undergoing . Our
results suggest that other loci may have the major causative roles in
ARNSHL in Iran.
Key words: Linkage analysis, ARNSHL, DFNB.