CYTOGENETIC FINDINGS IN MENTALLY
RETARDED IRANIAN PATIENTS Nasiri F1, Mahjoubi F1,2,*, Manouchehry F1, Razazian F1, Mortezapour F1, Rahnama M1 *Corresponding Author: Dr. Frouzandeh Mahjoubi, Genetics Department, Iran Blood Transfusion Organization
Research Centre, High Institute for Research and Education in Transfusion Medicine, Hemmat Express Way, Next to
the Milad Tower, Tehran, Iran; Tel.: +9821-44580389; Fax: +9821-44580399; E-mail: Frouz@ nigeb.ac.ir page: 29
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DISCUSSION
There is great variation in the frequency of the
reported chromosomal abnormalities found in MR
patients. A cytogenetic study of 419 MR school children
in southern Taiwan, by Shiue et al [2], found
chromosomal abnormalities in 22.43% of the cases,
with trisomy 21 occurring in 77 cases (18.38%). Sex
chromosome aneuploidies were found in three cases
(0.72%). Structural abnormalities of autosomes were
found in 13 cases (3.10%) (2). Another study of 341
MR children in Taiwan found chromosomal abnormalities
in 89 cases (20.3%) including 63 of trisomy
21 (10.7%) and 13 of fragile X (3.8%) [4].
Coco and Penchaszadeh [5] reported on a cytogenetic
study in 200 MR children in Argentina. They
found chromosomal abnormalities in 42 (21%) with
26 cases having structural chromosome defects [5].
Two studies were performed in The Netherlands.
One study done in Amsterdam (in the south of The
Netherlands) indicated that a chromosomal base in
22.1% of the patients was responsible for their MR.
Of these, 14.3% were Down’s syndrome patients,
and 6.1% had other chromosomal abnormalities [6].
Another study done in Amsterdam indicated that 20
patients had chromosomal anomalies (7.5%) in 266
karyotyped MR children. Interestingly, these were
mainly structural chromosome aberrations [7].
A study performed in Poland showed that the incidence
of abnormal karyotypes in MR patients was
10.1% [8]. However, the percentage of chromosome
aberrations found in patients with non specific mental
retardation was 2.2% [8]. A study done by Butler and
Singh [9] in America showed that 39 out of 201 (6.6%)
institutionalized MR patients had abnormal chromosome
with Down’s syndrome noted in 31 of the patients.
While the overall frequency of chromosomal
abnormalities in these reports was similar, there are
reports of either low or high percentages of chromosomal
aberrations in other studies. For example,
Celep et al. [10] reported the percentages of chromosomal
abnormalities in 457 Turkish MR Patients
to be only 4.81%. Chromosomal abnormalities and
polymorphisms were detected in 65 (14.21%) (structural
and numerical chromosomal abnormalities in 22
patients and polymorphisms in 43) of 457 MR and/
or multiple congenital anomaly (MCA) patients. On
the other hand, a study done in Slovakia revealed a
very high percentage of chromosome abnormalities
in MR patients. Of 324 MR patients, 104 (53.0%)
had chromosomal aberrations [11].
The differences between the incidences of chromosomal
abnormalities in the literature could be
caused by the criteria for patient selection, and the
techniques applied [cytogenetics only or in combination
with molecular cytogenetics such as fluorescent
in situ hybridization (FISH) and comparative genomic
hybridization (CGH)]. In our study of 865 screened
subjects, chromosomal anomalies were identified
in 205 of the patients (23.6%). The majority were
Down’s syndrome cases (n = 138, 15.9%). Interestingly,
we found three cases with marker chromosomes
(0.34%). Liehr and Weise [15] found that the
incidence of marker chromosomes is about 0.288%
in MR patients.
In general, van Karnebeek et al. [3] showed that
the mean yield of chromosome aberrations in classical
cytogenetics is about 9.5% (variation: 5.4% in
school populations to 13.3% in institute populations;
4.1% in borderline-mild MR to 13.3% in moderateprofound
MR; more frequent structural anomalies
in females). They also indicated that for fragile X
anomalies, yields were 5.4% (cytogenetic studies)
and 2.0% (molecular studies) [3].
The incidence of fragile X positive cases in our
study is slightly higher than some other reports although
we only employed cytogenetic tests for fragile
X. For example, Butler and Singh [9] reported 2.0%
fragile X positive in his cases, while in our study
it was 3.8%. Nevertheless, our results indicate that
the diagnostic contribution of the fragile X screening
could be considered equally important as conventional
chromosome banding techniques for the
detection of structural chromosome abnormalities.
Some of the chromosome aberrations were detected
in more than one case. For example: in two
cases, chromosome 2 was involved with a very close
breakpoint of q22 and q23 (Table 1; patients #1 and
#14); in two cases, chromosome 4 with breakpoints
p16 and p15.3 (Table 1; patients #5 and #15); and in another two cases, chromosome 6 with breakpoints
p25 and p23 (Table 1; patients #2 and #17). Even
more interesting, chromosome 11 in two cases and
chromosome 18 in another two cases had the same
breakpoints (Table 1; patients #6 and #16, and #4
and #23, respectively). This could be very interesting
because some of the genes responsible for MR
may be located in these breakpoints. For example,
the chromosomal breakpoints for the two MR patients
(patients #1 and #14) were at 2q22 and 2q23,
respectively. Heterozygous mutations or deletions
of the ZEB2 gene, which is located near to 2q22,
is known to be responsible for Mowat-Wilson syndrome,
with MR being one of the main features of
this syndrome (16). Furthermore, heterozygous mutations/
deletions of the DPAGT1 gene located at 11q 23
(the breakpoint for patients #6 and #16) may reduce
up to 88.0% of the mature mRNA and cause clinical
features including MR [17].
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