2009 Vienna - European Society of Human Genetics

Prenatal and perinatal genetics
developing RDS in neonates from Bashkortostan Republic, Russia.
The whole peripheral blood of 159 patients with respiratory disease
and umbilical cord blood of 299 healthy term neonates was used for
the isolation of genomic DNA. The patient group consisted of 3 subgroups
(63 neonates with pneumonia, 40 babies with RDS and 53 infectious
complicated RDS) The genomic DNA served for PCR in the
genotype analysis.
The results demonstrated that SFTPD (Met11Thr, Ala160Thr) gene
genotypes frequency distribution patterns not significantly differ
between patients with RDS and healthy neonates (χ 2 =2.68, df=2,
p=0.262; χ 2 =1.31, df=2, p=0.518).
The SFTPD Thr/Thr genotype is protective against the development
complication in RDS (7.5% vs. 32.5%; χ 2 =7.9, p=0.006; OR=0.17,
95%CI 0.04-0.64). Whereas, children with RDS who has the Met/Thr
genotype were susceptible to infectious complication (73.6% vs. 50%;
χ 2 =4.5, p=0.003; OR=2.79, 95%CI 1.07-7.32).
We suppose that the Met11Thr polymorphism of SFTPD gene may play
a significant role in the development of complicated RDS in neonates.
P05.32
Prenatal diagnosis of a fetus with ring chromosome 21
characterized by molecular cytogenetic methods
I. D. Papoulidis 1 , E. Siomou 1 , E. Manolakos 2 , T. Liehr 3 , A. Vetro 4 , A. P. Athanasiadis
5 , O. Zuffardi 4 , M. B. Petersen 1 ;
1 Eurogenetica S.A., Thessaloniki, Greece, 2 Bioiatriki, Athens, Greece, 3 Friedrich-Schiller-University,
Jena, Germany, 4 Universita di Pavia, Pavia, Italy, 5 Aristotle
University, Thessaloniki, Greece.
Ring chromosome 21 is a rare structural chromosomal abnormality
resulting, most of the times, from breakage in both arms of the chromosome
and subsequent fusion of the two ends. There is a wide spectrum
of phenotypes in ring 21 carriers that seems to be associated
with different breakpoints of 21p and q arms, but also with somatic loss
of the ring. Here we report a case of a fetus that was diagnosed with
mos46,XY,r(21)(p11.2q22)[34]/45,XY,-21[4]/46,XY[14] karyotype. Ultrasound
examination at 21 weeks’ gestation showed no abnormalities
and amniocentesis opted due to advanced maternal age. Cytogenetic
analysis was performed in the parents and showed the presence of the
ring chromosome in 1 out of 100 metaphases in the father, indicating
a possible familial transmission. Analysis by Fluorescent In Situ Hybridization
(FISH) and comparative genomic hybridization (aCGH) with
resolution of 144 kb showed no deletion or duplication. After genetic
counseling, the parents decided to continue the pregnancy and postnatal
examination just after birth found no congenital abnormalities.
P05.33
Robinow syndrome revealed during pregnancy on limb
anomalies
D. Meyran 1,2 , F. Escande 3 , A. Dieux-coeslier 1,2 , C. Chafiotte 4 , D. Thomas 1,5 , P.
Dufour 1,5 , J. Andrieux 1,6 , S. Manouvrier-Hanu 1,2 , M. Holder 1,2 ;
1 Jeanne de Flandre, Lille, France, 2 Clinical Genetics, Lille, France, 3 Centre de
Biologie Pathologie, Lille, France, 4 Radiologie, Lyon, France, 5 Maternity, Lille,
France, 6 Genomic platform, Lille, France.
Robinow syndrome is a rare disease characterised by the association
of mesomelic limb shortening, facial and genital anomalies. It can
be inherited in an autosomal dominant or recessive mode. Recessive
forms are severe and the result of ROR2 mutations, whereas the aetiology
of dominant forms remains unknown. We report a further case of
Robinow syndrome diagnosed at birth, with interesting prenatal findings.
Parents were healthy and not consanguineous. The mother was 39year-old.
The first trimester ultrasound showed an increased nuchal
translucency (2.7 mm). Karyotype on amniotic fluid was normal (46,
XX). The second trimester ultrasound revealed short ulna and radii (5 th
centile). A spiral CT scan revealed delayed ossification and a mesoaxial
polydactyly on both feet. A chondrodysplasia was suggested and
pregnancy was followed since no definite diagnosis could be realised.
The baby girl was born at 39WG with a normal weight and head circumference
but a decreased length (47 cm, 25 th centile). Characteristic
facial features were noted comprising hypertelorism, short upturned
nose and gum hypertrophy. Mesomelic limb shortening and bilateral
polydactyly of the feet were observed. Skeletal X-rays confirmed the
bilateral mesoaxial polydactyly, revealed bifid terminal phalanges of
both thumbs and did not show any vertebral anomalies. Cardiac, trans-
fontanellar, renal ultrasonography and eye examination were normal.
Robinow syndrome was then diagnosed.
ROR2 molecular analysis was normal. Array-CGH is pending.
Even though Robinow syndrome has, to our knowledge, never been
diagnosed during pregnancy on ultrasound findings, it should be suggested
on the association of short long bones and mesoaxial polydactyly.
P05.34
split hand-split foot malformation due to 10q24 duplication
identified during pregnancy on array-CGH
M. Holder-Espinasse 1 , A. Valat 2 , A. Mézel 3 , P. Bourgeot 4 , S. Manouvrier-
Hanu 1 , J. Andrieux 5 ;
1 Service de Génétique Clinique, Hôpital Jeanne de Flandre, Lille, France, 2 Service
de Gynécologie-Obstétrique, Centre Hospitalier, Lens, France, 3 Service de
Chirurgie orthopédique, Hôpital Jeanne de Flandre, Lille, France, 4 Service de
Gynécologie Obstétrique, Hôpital Jeanne de Flandre, Lille, France, 5 Laboratoire
de Génétique médicale, Hôpital Jeanne de Flandre, Lille, France.
Ectrodactyly or split hand-split foot malformation (SHFM) is a rare
condition that occurs in 1 in 8500-25000 newborns and accounts for
around 15 % of all limb reduction defects. SHFM is clinically heterogeneous
and can be either isolated, associated with other malformations
or part of syndromic entities. This condition is usually inherited
in an autosomal dominant manner and several loci have been identified.
Among them, SHFM3 has been located on 10q24 and the naturally
occurring Dactylaplasia mouse is the animal model for SHFM3 in
humans. Recently, 0.5 Mb tandem genomic duplications at chromosome
10q24 involving at least the DACTYLIN gene have been found
in SHFM3 patients. No point mutations in any of the genes residing
within the duplicated region have been reported so far, and it is still not
clear how this rearrangement leads to the SHFM3 phenotype. Indeed,
complex alterations of gene regulation mechanisms that would impair
limb morphogenesis are likely.
We report on the third pregnancy of healthy non consanguineous
parents presenting normal hands and feet. At 23WG, the routine ultrasound
scan identified a split hand-split foot malformation. Chromosomes
on amniotic fluid were normal 46XX and array-CGH shown a de
novo 400 kb 10q24.31q24.32 duplication, comprising 5 genes including
DACTYLIN. Reassuring genetic counselling was performed since
these forms of SHFM are isolated and non-syndromic. At birth, limb
anomalies were confirmed and corrective surgery performed.
To our knowledge, this is the first prenatal report of 10q24 duplication
in SHFM.
P05.35
Antenatal population carrier screening for spinal muscular
atrophy
S. Y. Lin, Y. N. Su, C. N. Lee;
National Taiwan University Hospital, Taipei, Taiwan.
Background
SMA is one of the most common autosomal recessive diseases with
a carrier frequency of approximately to 1 in 50. Due to the incidence
and severity of SMA and the availability of a carrier-screening test, we
embarked on a stepwise prenatal SMA carrier screening program in
Taiwan.
Methods
A total of 70,048 pregnant women participated in this carrier-screening
program from 2005 to 2008. In the first phase, we used DHPLC as the
single tool for genetic testing. In the second phase, we combined the
DHPLC and MLPA for the test. If a woman was found to be a SMA carrier,
her husband was asked to take the genetic test. If they both were
SMA carriers, prenatal genetic diagnosis was suggested.
Results
A total of 40,756 pregnant women received the single-tool screening;
1,726 (4.2%) were discovered to be at high risk of being SMA carriers.
Of these 1,726 couples, 62 husbands were also at high risk of being
SMA carriers. Five fetuses from these couples were affected SMA
cases. A total of 29,292 pregnant women received the combined tests;
the results showed 603 (2.1%) were SMA carriers; twenty husbands
were SMA carriers. Six fetuses from this group were affected SMA
cases. This screening program cost $401,202 US dollars to avoid a
SMA affected child being born.
Conclusion