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

Cytogenetics
letion in 5q33 in all members of the family. This finding may represent
a more severe manifestation of the mandibulofacial dysostosis. TCS
is a heterogeneous entity, and evaluation and counseling of affected
individuals should be undertaken with caution.
P0418. Partial trisomy 12p and deletion 5p: an overlap of
dysmorphic features
L. Morozin Pohovski, I. Barišić, I. Sansović, I. Petković;
Children’s Hospital Zagreb, Zagreb, Croatia.
We describe a 2-year and 11 month-old girl who presented with dysmorphic
facial features, short neck, supernumerary nipples, short
wide hands, clinodactyly of the fifth finger, postnatal growth retardation,
generalized hypotonia and developmental delay. Detailed clinical
examination did not reveal associated congenital malformations.
Cytogenetic evaluation on high resolution G banding showed aberrant
chromosome 5 in all metaphases. The karyotype was designated as 4
6,XX,der(5),t(5;12)(5p15.3;12p12.2)mat. Molecular analysis confirmed
deletion of subtelomere 5p and trisomy of subtelomere 12p.
A comparison of the clinical findings in our patient with previously described
cases of pure 12p trisomies is presented. Pure trisomy 12p
has a well delineated dysmorphic features and is often associated with
different major malformations. Our patient did not display these typical
features, phenotypic manifestations being more compatible with
monosomy 5p. Rare structural rearrangements may lead to complex
clinical presentations. Detailed clinical description of patients is needed
in order to delineate the phenotype and improve genotype-phenotype
correlation.
P0419. Newborn with partial trisomy 11q resulting from mother′s
t (11; 21) balanced translocation
S. Teofilova 1 , O. Miljanovic 1,2 ;
1 Center for Medical Genetics and Immunology - Clinical Center of Montenegro,
Podgorica, Montenegro, 2 Institute for Children’s Diseases - Clinical Center of
Montenegro, Podgorica, Montenegro.
There is small number of reported cases with partial trusomy 11q,
which do not result from the most frequently observed translocation in
humans: t (11; 22).
We report a female newborn, the first child in family, with phenotype
characteristic for partial 11q trisomy, present at birth: microcephaly,
hypertelorismus, short, broad nose, long, prominent philtrum, higharched
plate, retraction of the lower lip, microretrognatia, low set,
malformed ears, short neck, poor positioning of feet, wrinkled palm
and feet skin and muscular hypotonia. Peripheral blood chromosomal
analysis of index case and her family revealed partial trisomy 11q in
newborn, resulting from rare mother′s t (11; 21) balanced translocation.
Further investigation of mother′s family has shown that t (11; 21)
was not present at her parents.
The cytogenetic and clinical finding of index case and her family will
be presented.
P0420. DOWN SYNDROME IN A PATIENT WITH PARTIAL
TRISOMY 21 RESULTING FROM A RARE MATERNAL SHIFT
V. Malan 1 , M. Rio 2 , M. Pic 1 , S. Chevallier 1 , M. Vekemans 1 , O. Raoul 1 ;
1 Service de Cytogenetique, CH Necker Enfants Malades, Paris, France, 2 Service
de Génétique Médicale, CH Necker Enfants Malades, Paris, France.
Down syndrome results generally from the presence of an extra copy
of chromosome 21. Unbalanced translocations or abnormal recombinant
chromosomes resulting from a pericentric inversion have also
been observed. Here, we report on a child with a Down syndrome
phenotype carrying a partial trisomy 21q22 resulting from “aneusomie
de recombinaison” in a maternal shift. During pregnancy, the mother
underwent amniocentesis because of pyelectasy detected by ultrasound
examination. The fetal karyotype was considered as normal,
46,XY. At 5 years of age, due to a developmental delay, chromosomes
studies were performed. The karyotype revealed an unusual short
arm of one chromosome 21 suggesting the presence of extra genetic
material. Because of the Down syndrome phenotype, FISH studies
were performed using probes specific for the DSCR (Down Syndrome
Critical Region). A third signal was observed on one chromosome 21p.
Karyotypes of the parents as well as FISH studies were performed.
The mother was found to be a carrier of a DSCR insertion onto the
short arm of one chromosome 21. Shift or intrachromosomal insertion
results from a three-break event leading to transposition of a chromo-
12
somal segment to another position in the same chromosome. Here the
proband inherited an unbalanced recombinant chromosome following
a crossing over in the maternal shift chromosome. Shifts occurring in
the short arm of an acrocentric chromosome are rare. If the length of
the segment is small, rearrangement mimics a short arm heteromorphism
(pstk+). The present observation illustrates the importance of
investigating an unusual short arm of acrocentric chromosomes.
P0421. Refinement of unbalanced aberrations of chromosome 7
in two severely affected children by multicolor banding (MCB)
S. G. Vorsanova 1,2 , I. Y. Iourov 2,1 , T. Liehr 3 , V. V. Monakhov 2 , O. S. Kurinnaya 1 ,
Y. B. Yurov 2,1 ;
1 Institute of Pediatrics and Children Surgery, Roszdrav, Moscow, Russian Federation,
2 National Research Center of Mental Health, RAMS, Moscow, Russian
Federation, 3 Institute of Human Genetics and Anthropology, Jena, Germany.
Although conventional cytogenetic analysis permits the diagnosis of
the majority of chromosome aberrations, almost all of them require
precision by molecular cytogenetic techniques. Here, we report on the
application of MCB technique (FISH-based high-resolution multicolor
chromosome banding) to refine two chromosome abnormalities involving
chromosome 7 in two female children with severe mental retardation
and congenital malformations. Initial standard karyotyping by GTG
banding showed the first case to be a monosomy of chromosome 21
(45,XX,-21) and the second case to be a deletion of the chromosome
7 short arm, 46,XX,del(7)(p21p15). After the application of FISH with
a set of site-specific probes for chromosome 21 following by use of
whole-chromosome painting probes, the first case turned out to be an
unbalanced translocation between chromosomes 7 and 21, but the
breakpoints still were under question. To refine chromosomal aberrations
in these cases, an MCB approach with microdissection-derived
DNA probes for chromosomes 7 and 21 allowing painting of chromosomes
at 550-band-resolution was applied. Thus, the first case was
defined as partial monosomy 7q34-qter and 21pter-q22.13 due to an
unbalanced translocation t(7;21) or 45,XX,der(7)t(7;21)(q34;q22.13),-
21 and the second case was defined as 46,XX,del(7)(p21.2p15.2).
Hence, we concluded that MCB technique was efficient enough for
breakpoint precision in aforementioned cases. When seen in this
perspective, one can further suggest MCB approach to represent an
efficient tool for clinical molecular cytogenetics in addition to well-established
FISH protocols with site-specific probes or newly introduced
array CGH-based techniques. Supported in parts by INTAS.
P0422. Three unrelated cases with cryptic unbalanced
subtelomere translocations
R. Stoeva1 , M. Kirchhoff2 , I. Ivanov1 , P. Ganchevska1 , I. Popova1 , I. Stoev1 , M.
Stefanova1 ;
1 2 Medical University, Plovdiv, Bulgaria, Rigshospitalet, University of Copenhagen,
Denmark.
Unbalanced subtelomere chromosome rearrangements are a significant
cause of both isolated and familial mental retardation/multiple
congenital anomalies syndromes with approximately 5 to 10% of over
3000 affected individuals tested worldwide. Here we report three unrelated
cases with cryptic unbalanced translocations, t(1;11)(pter,qter),
t(4:11)(pter;qter) and t(8;20)(pter;pter). Disballances were found by
MLPA analyses. A combination of partial monosomy 1pter/trisomy
11qter was found in a one-month-old girl. She had a low birth weight,
microcephaly, telecanthus, long eye lashes, blue sclera, broad nasal
bridge, fleshy nose, smooth philtrum, down-turned corners of the
mouth, thin lips, high palate, posteriorly rotated dysplastic ears, short
neck, wide spaced nipples, abnormal dermatoglyphic patterns, long
overlapping toes, generalized hirsutism, caudal appendage and patent
ductus arteriosus. The second case, a two-month-old girl, presented
with partial trisomy 4pter/monosomy 11qter. She had pyloric stenosis,
thrombocytopenia, hepatosplenomegaly and following dysmorphic
features: face/body asymmetry, pronounced hypertelorism, strabismus,
wide nasal bridge, anteverted nostrils, high palate, midline cleft
tongue, low set-up ears, clinodactyly. This clinical presentation overlaps
previously described Paris-Trousseau type thrombocytopenia
(#188025) due to partial monosomy 11q. The third case, a five-year-old
girl, revealed partial monosomy 8pter/trisomy 20pter. She had mental
retardation, obesity, hydrocephaly and following dysmorphic features:
arched eyebrows, synophrys, tapering fingers, patchy skin depigmentation.
Genealogical follow-up revealed in two of the cases additional