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

Clinical genetics
Lithuania.
The aim was to investigate the incidence and type of orofacial clefts
(OCs) associated with congenital defects in Lithuanian population.
Patients and methods. There were included 235 cases of OCs with one
or more major congenital anomalies investigated from 1993 to 2005 in
the study. OCs were subdivided into three groups: cleft palate alone
(CP), cleft lip alone (CL) and cleft lip with cleft palate (CLP). Each case
was assigned to one of categories: nonchromosomal syndromes, OCs
with chromosomal anomalies and unidentified syndromic OCs with
one or more associated major anomalies, which were grouped according
British Pediatric Association Classification of Diseases.
Results. There were 70 cases of nonchromosomal syndromes (20 different
syndromes), 26 cases of OCs with different chromosomal abnormalities
and 141 non-syndromic patients with OCs and one or more
associated major anomalies of total 235 persons with OCs and additional
anomalies. There were 420 different anomalies in patients with
unidentified syndromic OCs, a mean of 2,9/proband. The commonest
organ system affected was the musculoskeletal system (133 anomalies),
followed by cardiovascular (90) and anomalies of face (including
eye and ear) and neck (64).
Conclusions: This study expanded the phenotype of patients with
OCs. According to the results of this study we can propose that all patients
with OCs should be examined by the team of specialists such as
pediatricians, plastic surgeons, orthodontists, cardiologists and others
with closer collaboration of clinical geneticists. A routine screening for
other associated malformations, especially skeletal, central nervous
system, and cardiac defects, is required.
P0212. Tunisian family with ocular, squelettal and abdominal
malformations
R. M‘rad1,2 , F. Maazoul1 , I. Chelly1 , M. Chaabouni1,2 , L. Kraoua1 , L. Ben jemaa1 ,
H. Chaabouni1 ;
1 2 department of human genetics, Charles Nicolle hospital Tunis, Tunisia, department
of human genetics, faculty of medicine Tunis, Tunisia.
We report on two sisters who had a unique association of facial, ocular
, skelettal defects and abdominal muscle hypoplasia. They are the
fourth and the fifth sibs, born to healthy first cousin parents originating
from Tunisia. The family history is unremarkable. The phenotypic findings
are compared with the previously reported patients referred to as
Carnevale, OSA, Michels and Malpuech syndromes. All are autosomal
recessive. We conclude that the present patients resemble most patients
with OSA syndrome previousely reported in 1996 by Mingnarelli
et al .
Despite the presence of apparently distinctive key features, it appears
that these four entities share multiple similarities in the facial and the
pattern of malformations.
P0213. Osteopetrosis mutation study among an Iranian family;
TCIRG1 gene
T. Majidizadeh 1 , M. Dehghan Manshadi 1 , M. Rostami 1 , K. Banihashemi 2 , S.
Akbaroghli 3 , M. Houshmand 1 ;
1 National Institute Center Genetics Engineering & Biotechnology, Tehran, Islamic
Republic of Iran, 2 GPEF, Ministry of Science, Research and Technology,
Tehran, Islamic Republic of Iran, 3 Iranian Behzisti Organization, Tehran, Islamic
Republic of Iran.
Autosomal-recessive osteopetrosis is a severe genetically heterogeneous
disorder due to osteoclast failure. Dense bones prone to fracture,
severe hematological failure, and neurological impairment are
among the prominent features of the disease.
It has been shown that mutations in the TCIRG1 gene may result in
three disaese phenotypes characterized as autosomal recessive, infantile
malignant and also in association with bone mass forms associated
with 38, 10 and 1 mutations respectively.
Previous studies showed that 19 out of total 50 known mutations (38%)
were splicing mutations, which may also be expected to be the most
common mutations in Iran.
In our study a family of 37 members was the subject of investigation for
TCIRG1 gene mutations for 3 cases of severe osteopetrosis after the
clinical diagnosis of the proband who have been involved with the disorder
through the first seven years of his life using the standard PCR
method for all 20 exons and then sequencing to detect the risk of next
pregnancies involvements in the parents of the dead proband.
P0214. Epidemiological study of some familial cases with
primary osteoporosis.
M. Cevei1 , D. Stoicanescu2 , M. Mihailov1 , D. Farcas1 ;
1University of Oradea, Faculty of Medicine and Pharmacy, Oradea, Romania,
2University of Medicine and Pharmacy, Timisoara, Romania.
Osteoporosis is a multifactorial disease characterized by a decrease
in bone mass and deterioration of bone architecture. Genetic factors
are determinants of peak bone mass and may influence age-related
decreases of bone mass. WHO has established an operational criterion
based on bone density measuring, the T-score. 122 cases were
studied, 51 diagnosed with primary osteoporosis. Mean age was 57.6
years. The main inclusion criterion was the acceptance of affected individuals
to participate in the study. Accurate family history was taken.
Daughters of affected persons were evaluated by DEXA technique.
67.2% of them had T-score values that indicated osteopenia or osteoporosis
(mean value -2.3SD). Molecular testing was not available. We
are interested in future collaborations. In conclusion, descendents of
affected parents are at a high risk for osteoporosis, important aspect
for primary prevention.
P0215. Otopalatodigital type I syndrome: report of a familial case
L. M. J. Albano1 , S. P. Robertson2 , L. A. N. Oliveira1 , D. R. Bertola1 , C. A. Kim1 ;
1 2 Instituto da Crianca, Sao Paulo, Brazil, Dept Paediatrics and Child Health,
Dunedin School of Medicine, Otago University, Dunedin, New Zealand.
Otopalatodigital syndrome spectrum disorders include four phenotypically
related conditions: otopalatodigital syndrome (OPD) type I and
II, frontometaphyseal dysplasia and Melnick-Needles syndrome . Mutations
in the FLNA gene have been reported in the majority of the
patients. Most pedigrees are consistent with X-linked inheritance. We
report on a typical OPD type I familial case, a 7y7mo-old boy presenting
characteristic dysmorphisms with prominent supraorbital ridges,
hypertelorism, submucous cleft palate, deafness, short broad thumbs,
spatulate finger tips, partial syndactily of the fingers, overlengthening
of the second toes and foreshortening of the great toes, broad terminal
phalanges of the other digits. His mother was considered normal with
normal stature (1.55m), without facial dysmorphism, exhibiting only bifid
uvula and longitudinal darkish lines striates on nails of the 1th , 2 th
and 3 th fingers, similar to the ones found in craniofrontonasal dysplasia.
They showed unimpaired intellect. A mutation in the FLNA gene
was detected in both mother and son. Our case reinforces the phenotypic
variability in OPD syndrome type I, and also the importance
of molecular analysis in mild phenotypes and in females to confirm a
carrier status, in order to perform a more precise genetic counseling.
P0216. Parkinsonism and essential tremor in a family with
pseudodominant inheritance of PARK2
F. E. Rocca1 , F. Annesi1 , P. Tarantino1 , I. C. Cirò Candiano1 , S. Carrideo1 , D.
Civitelli1 , M. T. Pellecchia2 , P. Barone2 , G. Provenzano1 , E. V. De Marco1 , G.
Squillace1 , V. Greco1 , G. Annesi1 ;
1 2 Institute of Neurological Sciences, Mangone (Cosenza), Italy, Department of
Neurological Sciences, University Federico II, Napoli, Italy.
The Parkin gene (park2) plays an important role in the early onset
forms of Parkinson’s disease (PD). Mutations in this gene have been
described in approximately 50% of familiar cases and in the 10-20% of
sporadic cases with an onset age ≤ 45 years. This study shows the results
of a parkin gene analysis in a family from Southern Italy.This family
included five affected individuals showing either essential tremor
(ET), parkinsonism, or both, consistent with pseudo-dominant inheritance
of PARK2. The affected patients were screened for mutations
in the parkin gene by a combination of gene dosage and sequencing
of entire coding region. We identified a 226 C>G homozygous missense
mutation leading to the amino acid substitution R42P in two
parkinsonian subjects and in 2 other not affected members of the family.
Four subjects carried the R42P substitution in heterozygotic form.
Exon rearrangements were excluded. Striatal dopamine transporter
density was reduced in accordance with phenotype and number of
mutated alleles. Apparently, this family did not show consanguinity, but
haplotype analysis revealed a common chromosomic region shared by
some members of both branches of the kindred, suggesting a single
founder. Whether postural and kinetic tremor in this family really represents
ET or is a first manifestation of parkinsonism requires further
follow-up. Nevertheless, we suggest that parkin mutations may have a
role in families with occurrence of both diseases.
2