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

Clinical genetics
due to iron storage resolving with time. Metabolic investigations and
karyotype were normal for both.
Analysis of these observations together with a review of previously
published cases suggests that patients suffering from tricho-hepatoenteric
syndrome and/or syndromic diarrhea actually present the same
heterogeneous disease that has been wrongly and confusingly separated
into 2 differents entities. The 5 mains signs are the same ( Low
birth weight, Intractable diarrhea, hair anomaly, facial dysmorphism
and immunological defect) and the cirrhosis is found inconsistently but
in both groups.
The acknowledgment that these two syndromes represent the same
disease is a crucial step toward a better description of this syndrome,
of its outcome and to set studies trying to identify a putative underlying
genetic defect.
P0147. Mild phenotype in a child with low-rate mosaic 11q
deletion
E. Sukarova-Angelovska, M. Kocova, N. Angelkova, G. Ilieva;
Pediatric Clinic, Skopje, The former Yugoslav Republic of Macedonia.
Monosomy of the long arm of chromosome 11 is a rare structural chromosomal
aberration with facial dysmorphism and severe mental retardation.
Folate-sensitive fragile site of this chromosome, located at
the band 11q23.3, facilitates breakage of this part of the chromosome.
Distal part of the chromosome is being lost, and causes characteristic
features of Jacobsen syndrome. Mosaic deletion of the chromosome
11q has rarely been reported.
We report on a girl aged 2 years with slight developmental delay. Facial
dysmorphism included bitemporal narrowing, prominent glabella,
hypertelorism, up-slanted eyes, short upturned nose and wide-opened
mouth. The height and head circumference were at the 3rd percentile
curve. Short arms and narrow thorax were present. Neurological evaluation
showed slight degree of hypotonia, but motor achievements were
satisfactory for the age. Speech delay was present. Ultrasound examination
of the heart showed atrial septal defect. Cerebral computed
tomography, renal studies and hematological evaluation were normal.
The karyotype was 46XX/46,XX,del(11)(q24-> qter) (90%/10%). The
parental karyograms were normal. This finding suggests a postzygotic
event resulting in a child with mild clinical findings of Jacobsen syndrome.
The follow-up of the child and genetic counseling is needed
since the mosaic cell line could be found in ovaries as well.
P0148. Johanson-Blizzard Syndrome - The importance of genetic
counseling and multi-disciplinary approach to rare diseases and
neurodevelopmental delay
B. Bozorgmehr, A. Karimi-Nejad, A. Mirblooki, M. H. Karimi-Nejad;
Kariminejad-Najmabadi Pathology & Genetics Center, 14665/154, Tehran,
Islamic Republic of Iran.
We are reporting a 11-month-old Iranian girl with Johanson-Blizzard
Syndrome, third offspring of first cousin parents. Their first and second
child died in the neonatal period due to midline scalp defect and secondary
infection. We believe they were also affected with Johanson-
Blizzard Syndrome. This syndrome is an extremely rare ectodermal
dysplastic disorder considered to be an autosomal ressecive disorder.
Each clinical manifestation has different differential diagnosis so
it shows the importance of genetic counseling to help the family. The
proband had growth and developmental delay, short stature, microcephaly,
hypoplastic alae nasi, scar of a repaired scalp defect, upsweeped
hair, hypothyroidism, deafness, and malabsorption, consistent
with Johanson-Blizzard Syndrome.
P0149. The birth prevalence of Joubert syndrome: a population
based study in the Netherlands.
H. Y. Kroes, D. E. Fransen van de Putte, C. J. Ravesloot, D. Lindhout;
Dept. of Medical Genetics, Utrecht, The Netherlands.
The Joubert syndrome (JBS) is a clinically variable and genetically
heterogeneous developmental brain disorder with autosomal recessive
inheritance. The birth prevalence of JBS, necessary for carrier
frequency calculation in genetic counseling, is not clear yet. We undertook
a nationwide survey of JBS in the Netherlands. Since 2002,
patients were systematically ascertained prospectively and retrospectively
from multiple sources.
A total of 54 patients were ascertained. The date of birth ranged from
1973 to 2005. Male:female ratio was 32:22. The number of newborn
JBS patients per year ranged between 0 and 2. Numbers increased
over the years, with a maximum and stable number of around 2 newborn
JBS patients per year from 1998 to 2005, probably due to improved
ascertainment. This renders a mean birth prevalence of JBS of
1 in 113,797 over the period 1998-2005. When also counting the uncertain
cases, the birth prevalence over this period was 1 in 83,850.
We conclude that, for practical purposes, a JBS birth prevalence of 1 in
100,000 can be used. This is considerably higher than the estimate of
1 in 258,000 by Flannery & Hudson in 2004. On the basis of the Hardy-
Weinberg equilibrium and the relative contribution of the different
genes involved in JBS, carrier frequencies can be calculated. For the
AHI1 gene, that was estimated to be responsible for 7 to 16 percent of
JBS cases, this results in a carrier frequency of 1 in 598 to 1 in 395.
P0150. BMPR1A gene mutations status in Polish JPS patients
M. Podralska 1 , W. Cichy 2 , E. Czkwanianc 3 , D. Nowakowska 4 , M. Teisseyre 5 , R.
Slomski 1 , A. Plawski 1 ;
1 Instytitute of Human Genetics, Poznan, Poland, 2 Karol Marcinkowski University
of Medical Sciences, Poznan, Poland, 3 Department of Pediatrics and Gastroenterology,
Institute of Polish Mother’s Memorial Hospital, Lodz, Poland, Lodz,
Poland, 4 Genetic Counseling Unit Cancer Center and Institute of Oncology,
Warsaw, Poland, 5 Department of Gastroenterology, Hepatology and Immunology,
The Children’s Memorial Health Institute, Warsaw, Poland.
The Juvenile Polyposis Syndrome (JPS), OMIM 174900 is an autosomal
dominant hamartoma polyposis syndrome predisposing to gastrointestinal
cancer. Autosomal dominant inheritance of the disease is
associated with the mutations in one of the tumor suppressor genes
MADH4 (mothers against decapentaplegic, drosophila, homolog of, 4)
or BMPR1A (bone morphogenetic protein receptor, type 1A). The JPS
is characterized by the occurrence of juvenile polyps in colon and upper
parts of the gastrointestinal tract, the average frequency of JPS
is 1:100000. The polyps occurring in childhood in most are the hamartoma
polyps. The solitary or not numerous and self-limited polyps
are not associated with the genetic predisposition. The characteristic
feature of the occurrence juvenile polyps is rectal bleeding what is an
indication for further diagnostics. The JPS encompasses the cases of
numerous polyps and/or a familial component. The characteristic feature
of the juvenile polyps are a markedly expanded lamina propria
containing dilated cystic glands, inflammatory cells, and prominent
stroma with a normal overlying epithelium.
The five juvenile polyposis patients were diagnosed in specialized
clinics. The recognition of the JPS syndrome in 3 cases was based
on observations over 100 juvenile polyps in colon and in two cases
on observation over 5 juvenile polyps in colon. The entire coding sequences
of the MADH4 and BMPR1A genes were sequenced by direct
PCR product sequencing. The novel BMPR1A gene mutations were
detected in three JPS families.
The study was financed by the Ministry of Education and Science, Poland,
grant number 2PO5E02630
P0151. A new case with homoplasmic mitohondrial mutation of
MT-ATP-6 and MCAD
M. K. Stancheva;
University Children Hospital, Sofia, Bulgaria.
The authors report a 2 year and 5 months old girl from second normal
pregnancy and delivery.Family history- grandmother with cerebral
stroke, with delay in psychomotor development, convulsions, hypotonia,
bilateral ptosis of eyelids, more pronounced at left, divergent alternating
strabismus, atrophy of nervi optici, complementary chordus in
left ventricle-variant of normal, hypoplasia of right ramus communicans
-variant of normal, selective metabolic screening showed MCAD and
investigation of mit. DNA / PCR-SBT method, showed polymorphisms,
C7028T/MT-CO1/, T 1700C/MT-RNR2, T 3197C/MT-RNR 2, A1479G/
MT-CYB/, A1146G, MT ND4, G11719A/MT-ND4/, A 8860G/MT-ATP6,
T9477A/MT-CO3/, T5495/MT-ND2, A16399G/D-loop/, A263G/D-loop,
309inc C/D-loop and homoplasmic mutation T8705CC in the gene of
MT-ATP 6, with aminoacid change methionin with treonin, with MRI
finding of delay in white matter and hiasmic atrophy.The reported child
is the fifth Case in Bulgaria with mitohondrial mutation of the MT-ATP6.
The mutation is not described in literature and has unknown effect on
mitohondrial function.The clinical picture is common in all cases .The
presence of MCAD will be further evaluated.