2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
both vasculites compared to the control (p = 0.001). G allele of G894T
polymorphism was found to be more frequent patients with vasculites
compared to the control (p = 0.001).
Conclusion: 4a/4b and G894T polymorphisms were appeared to be the
most informative traits helping differential diagnostics of both groups of
the vasculites (purples Shenlejna-Genoha and purples Schamberg).
P02.114
Antithrombin Ala383Pro: a new missense variant identified in a
patient with venous thrombosis
I. Tirado1 , M. Borrell1 , D. Llobet1 , I. Coll1 , C. Vallvé1 , P. Fuentes2 , E. Martínez-
Sánchez1 , J. Mateo1 , J. Fontcuberta1 ;
1Hospital Sant Pau Lab. Hematologia Unitat Hemostàsia i Trombosi, Barcelona,
Spain, 2Hospital Sant Pau Institut de Recerca, Barcelona, Spain.
Our aim was to study a new mutation in the SERPINC1 gene in a
patient with venous thrombosis. We performed analysis of Antithrombim
(AT) Cambridge II (SERPINC1 G13268T; p.Ala384Ser) using PCR
followed by digestion and it was confirmed by direct sequencing to
distinguish it from the AT Cambridge I (G13268C; p.Ala384Pro). We
determined functional AT (AT-f) and antigen AT (AT-Ag) and the mobility
of AT by crossed-immunoelectrophoresis (CIE) in the presence
of heparin. Also Protein C, Protein S, activated protein C resistance,
antiphospholipids antibodies, lupus anticoagulant, Factor V Leiden,
F2G20210A, F12C46T were determined. The patient had a qualitative
(type II) AT deficiency (AT-f:54%, AT-Ag: 95% with a normal heparin
binding pattern in CIE). The results suggested that proband was
a carrier of AT Cambridge. However, sequencing analysis revealed a
new genetic variant within exon 6 of the SERPINC1 gene, G13265C.
This mutation result in the exchange of residue Ala383 by a proline, 10
residues N-terminally of the Arg393-Ser394 scissile peptide bond located
in the reactive center loop and it was not detected in 100 healthy
subjects. It is likely that this phenotype is a substrate-like behaviour of
mutant AT molecules, as the bulkier proline residue would not be able
to insert rapidly into the main body of the serpin after thrombin/FXamediated
cleavage of the Arg393-Ser394 peptide bond. Moreover, the
presence of this new variant could interfere with the diagnosis of mutation
Antithrombin Cambridge II.
Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, RE-
CAVA (0014/0016)
P02.115
Waardenburg syndrome type ii: about 4 cases
L. Ben Jemaa 1 , H. Jilani 1 , H. Ben Mariem 1 , F. Maazoul 1 , R. Meddeb 1 , M. Chaabouni
1 , G. Besbes 2 , F. Tinsa 3 , M. Ferjaoui 4 , R. Mrad 1 , H. Chaabouni 1 ;
1 Service des maladies congénitales et héréditaires, Tunis, Tunisia, 2 Service
d’ORL EPS la rabta, Tunis, Tunisia, 3 Service de pédiatrie hôpital d’enfants,
Tunis, Tunisia, 4 Service D’ORL EPS Charles Nicolle, Tunis, Tunisia.
Waardenburg syndrome (WS) is a hereditary auditory-pigmentary syndrome,
the major symptoms being congenital sensorineural hearing
loss and pigmentary disturbance of eyes, hair and skin. Depending in
additional symptoms, WS can be classified into four types: WS type I
(WS1) is associated with facial deformity such as dystopia canthorum;
WS2 has no other symptoms; WS3 is associated with upper limb deformity;
and WS4, with megacolon.
It is an autosomal dominant affection which has a wide heterogeneity.
We describe here the clinical manifestations of 4 patients.
The first case was a familiar case in witch the father and his son have
congenital deafness, heterochromia irides, and a slight scoliosis.
The second case is an isolated case of a boy aged of 18 mounths, having
severe deafness, hypochromic iridis and ocular albinism.
In the last case we report an eight year-old boy who got a partial albinism
(white forelock, hypopigmented skin lesions) associated with
dysmorphic features and mental retardation. Audiometry was normal.
Our patients had clinical features compatible with Waardenburg syndrome
type II.
Type II Waardenburg are a heterogeneous group with normally located
canthi, sensorineural, hearing loss (77%) and heterochromia iridium
(47%).
Two genes are mutated in this form et should be screened.
P02.116
X-linked agammaglobulinemia: the underlying genetic defect in
three families
M. Cucuruz, E. Boeriu, L. Pop, M. Serban;
IIIrd Pediatric Clinic, Timisoara, Romania.
X-linked agammaglobulinemia (XLA) is a heritable immunodeficiency
disorder that is caused by a differentiation arrest in the bone marrow
resulting in severe B cell deficiency. It is caused by mutations in the
Bruton’s tyrosine kinase gene (Btk), that encodes a pathological tyrosine
kinase with a pivotal role in the life cycle of B cells. To date, more
than 550 mutations have been identified scattered along the entire
length of the Btk gene. We investigated three unrelated patients with
clinical diagnosis of XLA and their mothers for mutations in the Btk
gene. Two patients were found to have chain-termination mutations
in the kinase domain: a 4 bp deletion at positions 527-528 resulting in
frame shift and a premature termination codon at position 528, and a
nonsense mutation at codon 520 at the second patient. The third patient
has a missense mutation c.29T