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

Clinical genetics
fested progeroid features from infancy (OMIM 264090).
Proposita - 6 month age male is a single child of young healthy nonconsanguineous
couple (G1;P1). He was born at 38 weeks gestation,
labor was unremarkable (BW=2540; BL=47cm; OFC=34cm). Prenatal
hypoplasia and aged signs was present at birth. At age of 6 months
old progeroid appearance became more pronounced, patient showed
growth delay (W=4.6kg; L=60cm,; OFC=41cm all60 individuals of whom 15 are believed to be affected.
Fifty-three individuals are available for study, of whom 10 are affected.
Clinical evaluation has been completed for 17 individuals, of whom
eight are affected. Cutaneous signs were present in all affected individuals
and elastorrhexia was confirmed on lesional skin biopsy in one.
Most affected individuals have suffered cardiovascular complications
but there is no evidence of angioid streaks in these cases.
The evidence for AD inheritance in this family is overwhelming. They
may represent a variant of PXE without an ocular phenotype, and are
likely to provide evidence for genetic heterogeneity in this condition.
P0228. Association of PSORS1 genes with psoriasis in Russian
populations
E. Galimova, V. Akhmetova, E. Khusnutdinova;
Institute of Biochemistry ang Genetics, Ufa Scientific Center of Russian Academy
of Sciences, Ufa, Russian Federation.
Background: Psoriasis is a chronic inflammatory dermatosis affecting
approximately 0,3-5% world-wide. Numerous population-, family- and
twin-based studies point to a very strong genetic component of this disease.
Knowledge of the genetic factors leading to this disease will lead
to an understanding of the genetic, immune and pathogenetic aspects
of psoriasis. So far 9 psoriasis susceptibility loci have been identified
(PSORS1-9). The strongest genetic association has been found with
the HLA-C region (PSORS1) on chromosome 6p21. Altogether, eigth
genes are characterized in this completely sequenced region: HLA-C,
OTF3, TCF19, HCR, CDSN, SEEK, SPR1, STG. Aims: To assess the
genetic contribution of HCR single nucleotide polymorphisms (SNPs)
and HLA-C in the pathogenesis of psoriasis.
Methods: A case-control study with 400 psoriasis patients and 410
controls in Russian populations was conducted. All individuals were
genotyped for SNPs of HCR-305, 325, 477, 2327 and HLA-C association.
Results: Significant increase of the HLA-Cw6 allele was found in psoriasis
patients (44% vs.18%, OR=3.46, 95% CI 2.70-4.45, p=0.0005).
The frequencies of the HCR-325*T, HCR-2327*G alleles were significantly
increased in psoriasis patients compared with controls
(OR=3.61, p=0.005 and OR=2.45, p=0.0005, respectively). In subset
analysis there were no other significant differences in allelic frequencies
for the HCR-305G/A, HCR-477T/C polymorphisms.
Conclusions: Our results suggest that HLA-Cw6 remains the major risk
allele in Russian psoriatics, and that the HCR gene may play a role in
the development of psoriasis.
P0229. Radial hypoplasia in an infant with trisomy 18
G. Utine, K. Erdoğan, Y. Alanay, D. Aktaş, K. Boduroğlu, M. Alikaşifoğlu, E.
Tunçbilek;
Hacettepe University, Ankara, Turkey.
Trisomy 18 is a rather common autosomal trisomy with well-known
pattern of malformations. These include prenatal growth deficiency,
craniofacial dysmorphism, congenital heart disease, and overriding
fingers. A five-months old baby girl, referred for multiple congenital
anomalies including right radius hypoplasia and facial dysmorphic findings,
is presented. She was born at 34th gestational week with a birth
weight of 1900 gr (25th-50th percentile) as the second child of healthy
consanguineous parents. During the first month of life, she had feeding
problems. On physical examination, she was 54 cm, 3800 gr with
a head circumference of 37 cm (all below 3rd percentile). She had
thick eyebrows, wide and flat nasal bridge, bilateral epicanthic folds,
strabismus, a prominent philtrum and low-set ears. Facial asymmetry
with right facial microsomia was evident. Hypoplasia of the right ala
nasi and posterior rotation of the right ear were noted. She had rightsided
radial hypoplasia, hypoplastic right thumb, bilateral club feet and
overriding toes. Right side of the body appeared hyperpigmented as
compared to the other side. A systolic murmur of 2nd degree was present
and echocardiography revealed ventricular septal defect, patent
ductus arteriosus and pulmonary hypertension. Cranial MRI showed
mega cisterna magna. The karyotype was 47,XX,+18. The patient represents
an interesting presentation of trisomy 18, as radial aplasia and
other preaxial limb deficiencies are seen rarely in patients with trisomy
18.
P0230. Establishment of Rare Disease Services in the West
Midlands: Translation of Research into Routine Molecular
Diagnosis.
P. K. Rehal, J. Forsyth, E. Perrot, F. Macdonald;
West Midlands Regional Genetics Services, Birmingham, United Kingdom.
The West Midlands Regional Genetics laboratory has recently set up
routine services for a number or rare genetic disorders. These include
Wolfram syndrome (DIDMOAD), Combined Pituitary Hormone Deficiency
(CPHD), Sotos syndrome, Alstrom syndrome and CHARGE
syndrome. This is mainly due to the establishment of local clinical
expertise within these medical sub-specialities which has driven research
into these areas. Furthermore, guidelines set out by the UK Department
of Health with regard to test rationalization, reporting times
and increased automation have resulted in the production of a very
successful rapid high-throughput screening strategy, which is now applied
as a model for many new disorders within this laboratory.
The recent identification of genes involved in Micro syndrome, ARC
syndrome and Infantile Neuroaxonal Dystrophy by the closely linked
Medical Genetics Department has resulted in several requests for prenatal
diagnosis in advance of the establishment of a routine diagnostic
service.Results from interesting cases will be discussed together with
the challenges faced in the provision of rare disease services.