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BJMG 15/2 (2012) 29-34
10
...
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
...
ac
...
Chromosome anomalies were identified in 205
of the patients (23
...
The majority were Down’s
syndrome cases (n = 138)
...
The remainder (n =
34) had other chromosomal abnormalities including
structural chromosome aberrations (n = 23), marker
chromosomes with an unknown origin (n = 3), sex
chromosome aneuploidy (n = 6) and trisomy 18 (n
= 2)
...

Keywords: Chromosome abnormality, Idiopathic mental retardation (MR), Iranian patients
...

Mental retardation is found in individuals either as an
______________________________________________________________________

Genetics Department, Iran Blood Transfusion Organisation (IBTO)
Research Centre, High Institute for Research and Education in
Transfusion Medicine,Tehran, Iran
2
Clinical Genetics Department, National Research Institute of
Genetic Engineering and Biotechnology, Tehran, Iran
1

isolated finding, or as part of an underlying disorder
[1]
...
3%
[2]
...

It is known that numerical and structural chromosomal anomalies are one of the most common
causes of MR seen in these patients [4-12]
...
Mental retardation is the reason
for a substantial portion of referrals of patients and
families to the genetic counseling unit
...


MATERIALS AND METHODS
Blood samples were collected from 865 idiopathic MR patients who were refereed to IBTO for
cytogenetic study
...
The median age of the patients was 9
...

The patients enrolled in this study had unexplained
MR
...


29

CHROMOSOME STUDY IN MR PATIENTS

Chromosomal analysis was performed on phytohemagglutinin (PHA)-stimulated peripheral lymphocyte cultures of the patients using standard cytogenetic methods [13,14]
...

Briefly, peripheral blood lymphocytes were
cultured in 5 mL RPMI 1640 (Gibco®; Invitrogen,
Paisley, Scotland, UK), supplemented with 20%
(v/v) fetal bovine serum (GIBCO®; Invitrogen) and
10 µL/mL phytohemagglutinin (PHA) (GIBCO®;
Invitrogen) at 37°C
...
The cells were incubated at
37°C for about 10 mins
...
075 M) for about 20 mins
...
After
centrifugation, the cells resuspended in fixative (3v
methanol:1v acetic acid) (Merk, Frankfurt, Germany)
...

Using a Pasteur pipette, a drop was dropped onto the
slide
...
The chromosomes were treated with trypsin,
then stained with Giemsa (GTG-banded) after aging
...
A resolution of 450-band stage was
considered as a minimum; for a more detailed structural analysis, 550-700-band stage was preferred
...

For patients with structural chromosome abnormalities or marker chromosomes, a chromosome study of
the parents was recommended and performed if the
parents were alive and available (some of the patients
lived in orphanages) or cooperated
...
6%)
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9% of all the screened
MR cases, and 67
...
In 33 males, a positive fragile
X anomaly was found (3
...

The remainder (n = 34, 3
...
5% of the cases with chromosome
abnormalities) had other chromosomal abnormalities
(Table 1), mainly structural chromosome aberrations

Table 1
...

#

Familial/
De Novo

Sex-Age

Clinical Data (in addition to MR)

Karyotype (structural chromosomal anomalies)

1

F-9

developmental delay; history
of three sepsis cases in family
(probability of autosomal recessive
immunodeficiency); epicanthic fold

47,XX,del(2)(q22q32
...
2)[81]/46,XX,
del(2)(q22;q32
...
3)[18]/46,XX[33]

de novo

5

F-9

respiratory problems at birth;
cardiovascular problems; protrusion
of back of head and forehead bossing;
unable to hold neck erect; autism

46,XY,del(4)(p15
...
2)

de novo

7

M-7

open mouth; micrognathia; high arched
46,XY,del(22)(q11
...
5

developmental delay; epicanthic fold;
moon face

46,XX,del(5)(p15
...
2)

4

not known

Continue

30

BALKAN JOURNAL OF MEDICAL GENETICS
Nasiri F, Mahjoubi F, Manouchehry F, Razazian F, Mortezapour F, Rahnama M

Table 1
...
2)
brother: 46,XY,del(5)(p15
...
2;q11
...
21), –22
mother: 46,XX,t(7;22)(q36
...
1~11
...
2),+der(22)t(11;22)(q23;q11
...
2)
46,XX,inv(6)(p23p21)
mother: 46,XX,inv(6)(p23q21)
46,XY,inv(6)(q22
...
1)
father: 46,XY,inv(6)(q22
...
1)
46,XY,inv dup(10)(p11
...
3)
mother: 46,XY,inv(10)(p11
...
3)

not known
de novo
maternal
maternal
paternal
maternal

20

M-8

developmental dela; prominent nose;
speech and behavior problems

46,XY,add(15)(pter)

de novo

21

F-?

further clinical data not available

46,XX,add(15)(p13)

not known

frontal bossing; small jaw;
low-set ears; deepset eyes; strabismus;
drooping upper eyelid (left side);
22 M-14 mths
widely-spaced eyes; short nose;
long philtrum; downcurved upper lip;
camptodactyly; hypotonia

23

F-?

developmental delay; hypotonia in
hand and leg (power: 2/5); lack of
eye contact; dysmorphic features;
gastrointestinal reflex; cardiovascular
defects (oval fromen); small head
circumference; retarded growth;
edema in one foot; third toe of right
foot longer than the others; low breast
line; fever of unknown origin;
spcial nose feature

46,XY,dup(7)(q21
...
2qter)

de novo

Karyotype (numerical chromosomal anomalies)
1

M-19

developmental delay; minor
dysmorphic features

47,XY+mar[8]/46,XY[12]

de novo

2

F-15

primary amenorrhea

47,XXX[22]/46,X+mar[8]/48,XXX,+mar[2]/45,X[2]

de novo

3

F-8

further clinical data not available

47,XX,+mar

de novo

4

F-13
F-?

further clinical data not available

45,X(n=2)

de novo

5

M-7
M-21

further clinical data not available

48,XXYY(n=2)

de novo

6

M-19

further clinical data not available

47,XXY

de novo

7

M-3

further clinical data not available

48,XXXX/49,XXXXY

de novo

47,XY,+18(n=2)

de novo

8

M-3 mths some of the typical clinical symptoms
M-20 days of trisomy 18

31

CHROMOSOME STUDY IN MR PATIENTS

(n = 23)
...

In five cases parental chromosome study could not
be performed (patients #9, #10, #11, #14 and #21)
...
Sex chromosome aneuploidy
was detected in six patients
...


DISCUSSION
There is great variation in the frequency of the
reported chromosomal abnormalities found in MR
patients
...
43% of the cases,
with trisomy 21 occurring in 77 cases (18
...
Sex
chromosome aneuploidies were found in three cases
(0
...
Structural abnormalities of autosomes were
found in 13 cases (3
...
Another study of 341
MR children in Taiwan found chromosomal abnormalities in 89 cases (20
...
7%) and 13 of fragile X (3
...

Coco and Penchaszadeh [5] reported on a cytogenetic study in 200 MR children in Argentina
...

Two studies were performed in The Netherlands
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1% of the patients was responsible for their MR
...
3% were Down’s syndrome patients,
and 6
...

Another study done in Amsterdam indicated that 20
patients had chromosomal anomalies (7
...
Interestingly, these were
mainly structural chromosome aberrations [7]
...
1% [8]
...
2% [8]
...
6%)
institutionalized MR patients had abnormal chromosome with Down’s syndrome noted in 31 of the patients
...
For example,

32

Celep et al
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81%
...
21%) (structural and numerical chromosomal abnormalities in 22
patients and polymorphisms in 43) of 457 MR and/
or multiple congenital anomaly (MCA) patients
...
Of 324 MR patients, 104 (53
...

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)]
...
6%)
...
9%)
...
34%)
...
288%
in MR patients
...
[3] showed that
the mean yield of chromosome aberrations in classical cytogenetics is about 9
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4% in
school populations to 13
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1% in borderline-mild MR to 13
...
They also indicated that for fragile X
anomalies, yields were 5
...
0% (molecular studies) [3]
...
For example, Butler and Singh [9] reported 2
...
8%
...

Some of the chromosome aberrations were detected in more than one case
...
3 (Table 1; patients #5 and #15); and in

BALKAN JOURNAL OF MEDICAL GENETICS
Nasiri F, Mahjoubi F, Manouchehry F, Razazian F, Mortezapour F, Rahnama M

another two cases, chromosome 6 with breakpoints
p25 and p23 (Table 1; patients #2 and #17)
...
This could be very interesting because some of the genes responsible for MR
may be located in these breakpoints
...
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)
...
0% of the mature mRNA and cause clinical
features including MR [17]
...
Therefore, we recommend
cytogenetic analysis for every individual with idiopathic MR
...
In addition, by discovering the cause of
MR, e
...
, deletion or duplication/trisomy of a chromosomal segment resulting from a paternal/maternal
balanced translocation, prenatal diagnosis could be
applied for future pregnancies, thus preventing the
birth of another MR infant(s) through therapeutic
abortion, which is allowed in Iran
...


REFERENCES
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...
Mental
re­tar­dation in childhood: clinical and diagnostic profile in 100 children
...
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16(3): 239-248
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Chen YJ, Lin SJ, Kuo PL
...
J Formos Med Assoc
...

3
...
Diagnostic
investigations in individuals with mental retardation: a systematic literature review of their
usefulness
...
2005; 13(1): 6-25
...
Li SY, Tsai CC, Chou MY, Lin JK
...
Hum Genet
...

5
...
Cytogenetic findings
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...
1982; 12(2): 155-173
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Schreppers-Tijdink GA, Curfs LM, Wiegers A,
Kleczkowska A, Fryns JP
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The Hondsberg
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RC, Hoovers JM
...
J Med Genet
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...
Cytogenetic
studies in clinical diagnosis analysis of 1611 examination results
...
1995; 52(1): 5-9
...
Butler MG, Singh DN
...

J Intellect Disabil Res
...

10
...
Chromosomal abnormalities in 457 Turkish patients with
MCA/MR
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...
Srsen S, Misovicová N, Srsnová K, Volna J
...
Cesk Psychiatr
...

12
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Advances in molecular cytogenetics
for the evaluation of mental retardation
...
2003; 117C: 15-24
...
Gosden CM, Davidson C, Robertson M
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In: Rooney DE, Czepulkowski
BH, Eds
...
I: Constitutional Analysis
...
1992: 31-54
...
Benn PA, Perle MA
...
In: Rooney DE,
Czepulkowski BH, Eds
...
I: Constitutional
Analysis
...
1992: 91-118
...
Liehr T, Weise A
...
Int J Mol Med
...

16
...

Hirschsprung disease, microcephaly, mental

34

retardation, and characteristic facial features:
delineation of a new syndrome and identification of a locus at chromosome 2q22-q23
...
1998; 35(8): 617-623
...
Wu X, Rush JS, Karaoglu D, Krasnewich D,
Lubinsky MS, Waechter CJ, Gilmore R, Freeze
HH
...
Hum Mutat
...

18
...
Genomic
imbalances in mental retardation
...

2004; 43(4): 362-370

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