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

Clinical genetics
of the CSB gene. Molecular studies that followed led to the identification
of a novel insertion mutation c.1034-1035insT in exon 5 of the
CS-B gene. This mutation has been found in 1:20 healthy individuals
from the same village indicating a tremendously high carrier frequency.
Identification of the causative mutation might enable further characterization
of the CSB protein function in this unique family, as well as
prevention of this devastating disease among the population at risk
from this village.
P0059. Hepatic involvement in Cockayne syndrome type A
D. R. Bertola1 , G. Porta1 , M. P. Gonçalves1 , S. R. Cardoso1 , L. Suzuki1 , L. M. J.
Albano1 , R. A. Hegele2 , C. A. Kim1 ;
1 2 Instituto da Criança, São Paulo, Brazil, Robarts Research Institute, London,
ON, Canada.
Cockayne syndrome (CS) is a rare autosomal recessive disorder
characterized mainly by cachectic dwarfism, premature aging, mental
deficiency, microcephaly, intracranial calcifications, neurological
degeneration, retinal abnormalities and sensorineural hearing loss.
There are two subtypes: CS-A, the less common one, whose gene
responsible is called ERCC8 and CS-B, present in 75% of the cases
clinically diagnosed, whose gene responsible is ERCC6. These genes
show a pleiotropic effect, with several different organs and systems
involved. Gastrointestinal anomalies have been reported occasionally,
including especially elevated plasmatic levels of liver enzymes and
hepatoesplenomegaly. These abnormalities have been mild, unassociated
with jaundice or other clinical symptoms and have not involved
coagulation factors.
We describe the hepatic findings in a cohort of eight CS patients diagnosed
by molecular analysis as subtype A. One of our patients, a 12
year-old-girl, presented with recurrent gastrointestinal bleeding, due
to esophageal varices. The other seven patients, without any hepatic
signs/symptoms, showed elevated liver enzymes, ranging from slightly
higher than normal to very high levels. The bilirrubin levels and coagulation
studies were normal.
With better management of the individuals affected by CS, the survival
could be longer and problems, otherwise not recognized, may well be
of importance in this syndrome. The hepatic involvement could be,
sometimes, life threatening, as demonstrated in one of our patients.
Therefore, we recommend that all patients affected by CS should be
screened for hepatic involvement. It would be interesting to evaluate
hepatic involvement in patients affected by type B, in an attempt to
establish a genotype-phenotype correlation.
P0060. Clinical and molecular heterogeneity in Italian patients
affected by Cohen syndrome.
E. Katzaki 1 , I. Longo 1 , C. Pescucci 1 , F. Papa 1 , F. Ariani 1 , I. Meloni 1 , M. Priolo 2 ,
A. Selicorni 3 , R. Fischetto 4 , M. Celle 5 , R. Grasso 6 , B. Dallapiccola 7 , M. Bordignon
8 , R. Tenconi 8 , F. Mari 1 , A. Renieri 1 ;
1 Medical Genetics, University of Siena, Italy, 2 Medical Genetics Hospital of
Reggio Calabria, Reggio Calabria, Italy, 3 Pediatrics Unit, University of Milan,
Italy, 4 Citogenetics Unit , Giovanni XXIII Hospital, Bari, Italy, 5 G. Gaslini Istitute,
University of Genova, Italy, 6 IRCCS MEDEA, Bosisio Parini Lecco, Italy, 7 Medical
Genetics, University of Rome, Italy, 8 Clinical Genetics and Epidemiology,
University of Padova, Italy.
Cohen syndrome is an autosomal recessive disorder with variability
in the clinical manifestations, characterized by developmental delay,
visual disability, facial dysmorphisms and intermittent neutropenia. We
describe a cohort of 11 patients affected by Cohen syndrome from 10
Italian families and between 5 and 52 years of age at assessment.
Characteristic age related facial changes are well documented. Eyes
anomalies are found in 10/11 patients (retinopathy in 10/11 and myopia
in 6/11). Truncal obesity is present in 9/11 patients. DNA samples from
all patients were analyzed for mutations in COH1 by Denaturing High
Performance Liquid Chromatography (DHPLC). We detected fifteen
COH1 mutations; most of them are truncating mutations, only 2 being
missense changes in functional domains. Gene deletions were found
in two alleles. All mutations except one are private. A single base deletion
leading to p.T3708fs3769 was found, in heterozygous state, in
three apparently unrelated families deriving from a restricted area of
the Veneto’s lowland, between Padova and Tagliamento. Given the
geographical conformation of this region, a recent origin of the mutation
could be hypothesized.
Table 1 Summary of the clinical findings and COH1 detected mutations
Case
Clinical findings
1 2 3 4 5 6 7 8 9 10a 10b
Sex F M M M M F M M M F F
Consanguineus
parents
No No No No No No No No Yes No No
Age of assesment 10y 17y 18y 30y 5y 24y 5y 12y 6y 52y 51y
OFC at birth 5 25