2008 Barcelona - European Society of Human Genetics

Clinical genetics
17 PKU patients following dietary intervention coupled with multivitamin
supplementation . Data were compared to those of their matched
normal controls. PKU patients have marginal vitamin A deficiency (
mean plasma level ; 25 .2+/-6 .62ug/dl versus 48 .5+/-10 .1ug /dl of
control;highly significant (p>0.0001). Mean plasma levels of B-carotene
was also less than that of controls with a highly significant difference
(50 .65+/-15 .37ug/dl vs . 75 .80+/-19 .60 ug /dl; pG . These
brothers represent unique cases of propionic acidaemia with initially
normal cardiac function . This presentation of metabolic cardiomyopathy
may be amenable to medical therapy if detected before irreversible
cardiomyopathy has occurred .
P01.049
Novel mutations in AtP7B gene detected in patients with Wilson
disease from Bashkortostan
A. Magzhanova 1 , A. Karunas 2 , R. Magzhanov 1 , E. Khusnutdinova 2 ;
1 Bashkirian State Medical University, Ufa, Russian Federation, 2 Insitute of
Biochemistry&Genetics of Ufa Scientific Center Russian Academy Science,
Ufa, Russian Federation.
Wilson disease is an autosomal recessive disorder of hepatic copper
metabolism caused by mutation in the gene encoding a copper-transporting
P-type ATPase (13q14 .3-q21 .1) and leading to heavy hepatic
and neurological disorders . The purpose of this research was the analysis
of correlation between clinical features (neurological, neuropsychological
and liver disorders) and types of mutations .
We observed 71 patients and 96 members of their families from Bashkortostan,
using clinical examination, biochemical analyses of blood
and instrumental methods (hepatic scanning, hepatography) .
We had carried mutation analysis in 28 families with WD from Bashkortostan
.
Using SSCP analysis followed by sequencing 19 exons (2,3,4,5,6,7
,8,9,10,11,12,13,14,15,16,17,18,19,20) of ATP7B gene were identified
8 mutations and 3 polymorphisms in 83,9 % of chromosomes.
We have detected 2 novel mutations: Ala718Pro and Lys1315_Arg-
1316delinsGlu . The most common mutation in Bashkortostan were
His1069Gln - 48,2% and Lys1315_Arg1316delinsGlu - 10,7% .We
found correlation between type of mutation and clinical manifestations .
Patients with new deletion had more severe clinics with early manifestation
and hard liver disorders .
P01.050
Functional characterization of 4 cBs mutations found in
homocystinuric patients
M. Cozar1,2 , C. Esteves1 , R. Urreizti1,2 , D. Grinberg1,2 , S. Balcells1,2 ;
1Departament de Genetica; IBUB, Universitat de Barcelona, Barcelona, Spain,
2Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBER-
ER), ISCIII, Barcelona, Spain.
Homocystinuria due to CBS deficiency (MIM#236200) is a rare autosomal
recessive disorder characterized by extremely elevated levels
of homocysteine (Hcy) in plasma . More than 140 different mutations
have been described worldwide and near 1/3 of these mutations have
been heterologously expressed and tested for CBS activity . In the Iberian
Peninsula and South America the p .T191M mutation is particularly
prevalent and accounts for approximately 50-70% of the alleles . The
remaining mutations are found in a few pedigrees being mostly private .
We had found 3 new mutations (p .M173del, p .P200L and p .D281N)
and a previously described one (p .P49L) in four homocistinuric patients
(tree Spanish and one Indian) .
With the aim to assess the pathogenicity of these mutations they were
expressed heterologously in E. coli and their enzyme activities were
assayed in vitro, both in the absence and presence of the CBS activators
PLP and SAM . The wild-type CBS activity in the presence of
PLP was taken as reference (100%) . The expression of the mutant
proteins was confirmed by Western-blotting in denaturing conditions.
Mutations p .M173del and p .D281N showed null activity and a complete
lack of response to the activators, confirming their pathogenicity,
whereas p .P49L and p .P200L exhibited activities close to 30% and a
strong response to PLP . Furthermore, p .P200L showed good response
to SAM . These mutations were found in two patients with a mild phenotype
. Mutation p .P49L was found, in combination with p .R125Q, in a
53 year-old male who presented with a stroke and in his asymptomatic
51 year-old sister .
P01.051
Hereditary hyperferritinemia cataract syndrome: characterization
of two mutations in the L-ferritin gene
O. M. Messina-Baas 1 , L. M. Gonzalez-Huerta 2 , V. Ramirez-Sanchez 1 , S. A.
Cuevas-Covarrubias 3 ;
1 Hospita General de Mexico, Mexico D.F., Mexico, 2 Hospital General de Mexico,
Mexico D.F., Mexico, 3 Hospita General de Mexico, Fac Medicina, UNAM,
Mexico D.F., Mexico.
Hereditary hyperferritinemia cataract syndrome, an autosomal dominant
disease, is characterized by early onset bilateral cataract . Affected
individuals show high levels of serum ferritin without iron overload .
Elevated serum ferritin results from misregulation of L-ferritin transla-