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Genetic Research Centre, Mumbai
Institute Profile
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Objectives
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To carry out clinical and
operational research programmes so that early detection of genetic disorders
and appropriate interventional strategies can be implemented for optimal
health care
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Prevention of common birth defects and Thalassaemia by screening through
ultrasonography, maternal serum markers and HbA2 estimations
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To develop and validate newer
methods of diagnosis
ELISA for HbA2 –ß Thalassaemia
An immunocytochemical assay—FXS
FISH and CGH technology for
cryptic chromosomal
rearrangements and micro deletions
of chromosome 22 for CHD.
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The
unit of medical genetic was established in 1976 at the Institute for Research in
Reproduction . The unit was made an independent center of ICMR in 1986 and was
than lodged at the Bai Jerbai Wadia Hospital for children until end of 1999.It
was shifted back and located back at the Institute of Research in
Reproduction. Since its inception the center has catered to the needs of
families having children with mental retardation and multiple malformations. The
major activity of the center is to run an effective clinic where couples are
counselled regarding recurrence risk of genetic disorders and availability of
prenatal diagnosis.
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Departmental
Structure of the Institute - Diagram
(Flow Chart)
Structure of Center
Scientific Technical
Accounts
Deputy Director Research Assistant
Technical
Assistant
Technicians
Medical Social
Worker
Clinic Nurse
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Departmental structure |
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Clinical
Laboratory |
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Laboratory
facilities
The laboratory is well equipped to handle classic cytogenetic techniques
Fluorescent in-situ hybridization (FISH), Polymearse Chain Reaction (PCR),
Sonography and estimation of various maternal serum markers for chromosomal
disorders and neural tube defect.
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Clinical
facilities
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Genetic counselling,
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Prenatal diagnosis and
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Maternal and child health care,
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Teaching and training para medics.
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Education and
Training programme
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The center regularly takes for SNDT B.Sc and M.Sc. nursing staff,
educational manual and pamphlets for doctors and paramedical staff and also
for public awareness.
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Has organized WHO Sponsored Workshop on Management of Genetic disorders
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Has organized WHO sponsored Workshop on Reproductive
and Genetic Toxicology
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Epidemiological studies undertaken by the center
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Multi centric study on genetic causes of mental retardation in India
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Birth defect surveillance programme
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Impact of Genetic counselling
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Role
of preconception vitamins in prevention of Neural Tube defects
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Anthropometrics measurements of complex anatomic areas in Indian population
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New
chromosomal syndromes
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Feasibility of Introducing genetic services in national family welfare
programmes
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Development and validation of an ELISA of Hemoglobin A2
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Mutational analysis of Fragile X syndrome
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Screening for microdeletion in patient with associated with congenital heart
disease
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Mutational analysis of SRY in XY females
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Cryptic chromosomal rearrangements in couple with recurrent spontaneous abortion
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Multicentric study on genetic cause of mental
retardation in India
A study of 1314 children with mental retardation (MR)
without an obvious environmental cause was carried out at Banglore , Bombay,
Delhi and Lucknow
To determine the extent and pattern of genetic causes of
mental retardation in different parts of India. In all 42.3 per cent patients
had mild,25.3 per cent moderate, 19.2 per cent severe and 13.1 per cent profound
mental retardation. Among 1314 patients the chromosomal anomalies were found in
23.7 per cent, metabolic defects in 5.0 per cent and an identificable genetic
syndrome in 11.6 per cent of the patients. In the remaining 59.7 per cent
patients, no known genetic cause could be identified. However 66.5 per cent of
these patients had one or more of the following conditions (i) congenital
malformation with or without neurological deficit. (ii) history of
consanguinity, (iii) positive family history of mental retardation or (iv) a
positive screening test but without a confirmed diagnosis of metabolic defect
(suggesting that there may be additional unidentified genetic causes of mental
retardation.
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Genetic Counselling
The study was conducted
at 5 different centres. The data was collected and analyzed regarding the
perception of genetic disorders present in our people, the relative severity of
various problems which they face due to occurrence of a genetic disorder and the
expectations with which they come to the genetic center, The problems which a
genetic counselor faces during the counselling, the rapport which he establishes
were also assessed.
This project was
undertaken with following aims in mind.
(A)
To collect
information regarding consultands at 5 different regions of the
country in order to assess
1.
The
knowledge of the genetic disorders.
2.
The problems
consultands face after the birth of the child with a genetic disorder,
3.
The
solutions consultands seek when they come to the genetic
(B)
To estimate
the difficulties that counselor encounters during counselling.
(C)
To evaluate
the impact of counselling from the point of view of
1.
Understanding of the disorder by consultand.
2.
Helping
consultands decide whether to take a chance for the next issue or not.
3.
Choice of
options by consultands.
4.
Effect of
counselling on the problems faced by consultands.
5.
Relationship
of the counselor and the consultands.
A
detailed questionnaire was arrived at by consensus of geneticists,
pediatricians,physicians, sociologists and administrators. The consultands were
chosen randomly from the cases attending the genetic clinics. After enrolling as
per the patient, the questionnaire was filled as per the enclosed sheets.
The post
counselling evaluation was done when the consultands came for follow up. If they
failed to turn up, they were actively contacted at home and interrogated. In all
429 subjects completed the questionnaire and came for post counselling
evaluation.
Majority of the time couples approached the center together. Consultant came
from all religious. Mother mostly were housewife’s while fathers were skilled
workers or service class.
The
commonest problem in the child was mental retardation followed by defects in the
physical development and congenital anomalies. Nearly a quarter of the couples
had married their cousins, Around 70% of the disorders for which counselling was
provided was hereditary. Since the tests were available a large majority decided
to have another baby.
As can
be seen from consultands had very sketchy knowledge about the particular genetic
disorder which they had encountered. Only 52.28% knew the name
of the problem correctly. Only 17.64% of the consultands could not describe the
problem. This incidates that day to day contact with affected child had made
people observe things. The most important finding was that only 13,95 % of
people could tell the inheritance correctly. Majority of the consultands were
not sure whether the disorder was inherited or not. The fact that only 7.14% of
people could tell the recurrence risk correctly means that the knowledge of
genetics has not percolated to the majority of thee population or they were not
able to grasp the basic things about genetics, even though 1/3rd of
consultands were counselled by someone else before counselling in this project.
This is a significant finding.
Similarly, blame for the particular disorder was very rarely put on the genetic
basis. Majority of the couples had no idea about the causation. The fatalistic
attitude of the consultands is evident as the most commo factor that was
blamed was luck, chance or God’s will.
Probably
because of this assumption, consultands most commonly that one of them was
responsible for the occurrence of the disorder (67.3%). Both of them shared the
burden rarely. Single partners was blamed in 17 cases, out of which 15 were
mothers. This indicated the prevalent social custom of blaming the women.
Correspondingly, feeling of guilt was also rarely admitted by the consultands
(29.06%), Majority had no feeling of guilt.
Most of
the consultands confided that the emotional problems due to the birth of the
affected child were most difficult to face. Financial problems were next in the
order of severity. Telling relatives and friends or taking care of other
children was slight or no problem for most of them, while in almost 50% of
people there were problems in husband/wife relationship. Majority of them
thought that getting treatment for the affected child was no problem. According
to most of the consultands birth of an affected child had no effect on social
image or social life.
Majority
of the disorders for who counselling was done in this project were hereditary
970.19%). Counsellors from all centres observed that the prognosis of the
disorder was almost always average or poor. It was good in only 10.85% of
cases. Counsellors assiduously tried they explain the basic meaning of the
terms heredity., genes, chromosome risk of recurrence and chance. They did felt
that a small fraction of consultands only. Counselllors felt that a small
fraction of consultands were not capable of understanding these points. Except
for chance, these basic principles at best were partially understood; while only
7.69% of consultands could not grasp the idea of chance at all.
The
commonest options that were discussed were antenatal diagnosis, MTP and
preconception prevention. Counsellors were less inclined to discuss Adoption or
Artificial Insemination as the solutions of the problem.
Counsellors felt that the rapport established with consultands was excellent.
Co-operation during the session was poor in only 2% of cases, while “ease of
communication” was difficult in 15% of occasions and very difficult in none.
To
summarise the counselors agreed that generally the process of communication was
unhindered. Previous records were available, so that problems in diagnosis were
less. They felt that basic principles of co-operation and ease of communication
was fairly achieved.
The
exercise of genetic counselling will be in vain if one does not have the
feedback from the consutlands, Post counselling evaluation was performed most
commonly between second and the fifth month after the counselling session (
882.10%). The persons in whom the consultands confided were also noted. The
problem was most commonly discussed with the spouse by social worker and family
doctor were also entrusted with the problem. Relatives and friends were told
about the problem rarely.
Post
counselling evaluation clearly showed that the understanding of the disorder by
the consultands had increased markedly after the counselling session. After the
counselling session 40 % more people had some idea about the name of the
disorder. 72.95% people could describe the problem correctly ; compared to 45.74
% before the counselling and 30.66% of consultands had vague notions before
counselling .There was considerable improvement in remembering the chance of
recurrence (56.02%) post counselling as compared to 7.41% precounselling. Thus
there was definite improvement in the understanding of the disorder after
counselling.
Prior to
counselling 67.35% of consultands felt that none of them was responsible for the
disease. This figure rose to 88.5% after counselling. The blame put on mother as
the responsible person also decreased after counselling.
During
postcounselling evaluation it was clear that the understanding of the
consultands about the options open to them as described during the counselling
had increased remarkably. Antenatal diagnosis was the most discussed option.
Only on one occasion the consultands failed to understand the counselor and in
only one instance they failed to remember what was told. This never occurred
with other options viz. MTP and preconceptional prevention etc. This clearly
indicated that the consultands avidly retained the information regarding the
future plan of action.
Prior to
counselling most significant problems according to the consultands were
emotional, financial and problems in husband/wife relationship. It was pleasant
to note that the severity of financial problems was significantly less after
counselling (55.6%) pre and 33.54 % post) while emotional problem was still as
gloomy if not more than in
pre
counselling state.
Prior to
counselling almost half of the couples had some problems or other in
husband/wife relationship. In post counselling evaluation it was revealed that
56.6% of the consultands felt that counselling had positively improved their
married life. Only 2.5% of the consultands felt that counselling had negative
effect on their married life.
Counselling was remarkably successful in reducing the burden of guilt. 45.23% of
consultands felt that their feeling of guilt was less. But a disturbing finding
was that in 30.95% of consultands, the guilty feeling increased after the
knowledge of disease.
In
conclusion, the overall effect of counselling as perceived by the consultands
was quite satisfactory. 71.72% consultands experience that counselling
definitely helped them in coping with the situation.
The
counselors were blessed with good fortune to establish a happy and smooth
relationship with consultands. The communication was almost always conducted in
a congenial and receptive atmosphere. The consultands felt that most common
cause for not understanding the counselor was complexity of technical terms.
!3.06% experienced language problems during the communication. Only in 2
instances (1.14%) the counselors failed to establish good rapport. Emotional
problems and lack of curiosity or indifference was encountered in one case.
That the counselor spent adequate time for counselling is supported by the fact
that lack of time was never put forth as a reason for failing to understand the
communication. The counselors were almost always able to fulfill the
expectations of the consultands. This is proved by the fact that during
evaluation only 1.5% of consultands thought that they did not receive any
information, while 50% of them felt that they have received all information was
received during counselling. When consultands did not receive all the
information which they wanted, most commonly (45.24%) they thought that this was
due to inadequacies of present medical knowledge. 22.62% felt that counselor has
to get more information. About 16% of them felt that counselor did not want to
answer their questions or they failed to discuss a few facts which they wanted
answers for 2/3rd of the consultands wished to see the same counselor
again. This also is a proof of the good rapport established by the counselor. It
was noteworthy that about 20% of couples did not want to take any counselor
again. This is due to the gloomy future which a disorder may possess.
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New Chromosomal Syndromes
This Task
Force was initiated to reveal greater degree of resolution of chromosomes by
using high resolution of chromosomes by using high resolution banding technique
described by Yunis. Advances in processing chromosomes by variation in
harvesting and staining have in the past improved accuracy in diagnosis of
chromosomal abnormalities. The main aim of project was to use above technique in
precise diagnosis of patients with undifferentiated genetic disorder. Patients
who had mental retardation with more than two dysmoprhic features excluding
Downs syndrome, Turner and Klinefelter Syndorme were selected. Cytogenetic
studies were carried out using standard High Resolution Banding techniques as
well as using Ethidium Bromide technique. With this method we could get cell
synchronization and chromosome length to the 800-850 band stage. However, the
mitotic index being poor G-banding was not achieved. This method can be applied
only when precise location of bands are required. 107 patients blood was
processed using ethidium bromide method,10 of these showed chromosomal
aberration.
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Birth Defect Surveillance
Programme
17,653 consecutive newborns were examined at birth
for the presence of congenital malformation. The overall incidence of congenital
malformations was 1.6%. The central nervous system was most commonly involved.
There was a higher rate of malformation to mothers above 35 years. The incidence
of congenital malformation at birth was higher in still born and low birth
weight babies. Polygenic traits accounted for 45.1% while a chromosomal etiology
was found in 4%. 65.4% of the cases had genetic basis.
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Anthropometrics measurement of complex anatomic areas in Indian population
Anthropometrics had become
an important tool in the study of genetic conditions particularly as a
diagnostic aid forth the clinical genetics. The immediate objective of this kind
of research is for diagnosis development of pattern profile which will separate
affected individual from normal.
Anthropometric
studies have been conducted at several centres abroad, however in India there
are no such studies whereby 32 different body measurements were taken. With this
in mind ICMR had undertaken a project to develop norms of different
anthropometrics measurements in children from 3 months –14 years. Documentation
of various anthropometric measurements of anatomic areas in Indian population is
important for delineating syndromes typical to Indian population.
The project got underway
in December 1988 and till August 1992 we examined 1200 children for
anthropometrics measurements either in well baby clinic or various schools.
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Role of preconception vitamins
in the prevention of Neural Tube Defects.
It has been suspected that diet has a role in the
causation of neural tube defects. Several studies suggested that folic acid or
other vitamins might reduce the risk of recurrence but the studies were
inconclusive. A multicentric double blind randomized trial involving five
centres was planned. Women with a previous pregnancy affected by a neural tube
defect were eligible for the study. Women in trial were asked to take one tablet
daily from date of randomization until pregnancy was confirmed. Blood and urine
samples were collected at enrolment and supplementation on sex ratio, birth
weight and twinning rate. However, number of spontaneous abortions in the
vitamin group (4.4%) were less than those in placibo group (10%). This
incidental findings may deserve to be investigated further. No significant side
effect or toxic effect of supplementation with therapeutic dose of folic acid (4
mg per day) without simultaneous supplementation with B12 was observed. It was
clear from pooled data of all five centres that preconceptional folic acid
helped to prevent the birth of children with neural tube defect.
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Feasibility
of Introducing genetic services in the National Family Welfare Programme
Phase I and Phase II
Phase I
The objective of
the screening was to identify through markers,in maternal blood, a group of
woman at increased risk of having a pregnancy affected by a serious fetal
anomaly i.e. Neural Tube Defect and Thalassaemia and improve pregnancy outcome
through genetic screening. A study was initiated at Thane Civil Hospital for
Bombay area. A 1000 pregnant women in the first and second trimester attending
the antenatal clinic between 13-24 weeks were registered by us and included in
the study. A clinic screening proforma was filled up for all these women. Blood
was collected and screened for Thalassaemia carrier status and maternal serum
alpha feto protein levels were estimated for Neural tube defect.
100 primes were
studied for their TORCH status. A total of 1000 pregnant women were screened for
neural tube defects and beta Thalassaemia carrier status. Of the 26.9% of women
at risk for genetic diseases 7.8% were at risk for neural tube defects and 4.3 %
for Down Syndrome. Beta Thalassaemia carrier rate was 39/1000 i.e. 3.9% neural
tube defects were found in 11/1000.
Phase II
After running
genetic screening for 3 years it was now time for the local doctors to gradually
take over this screening programme.
To suggest
an intervention strategy we had to know the lacunae in existing knowledge
amongst doctors, interns, nurses, health visitor, ANM and social workers. A
simple questionnaire was set and given to the paramedical staff and medical
staff. Another simple questionnaire was prepared for the patients to note their
reactions to this scheme. The results of this initial survey brought to light
the fact that 80% of paramedics were not clear about genetic tests while around
50% of medical doctors could answer the questions related to genetics. Since
most patients had no history of any disorder they were not aware of prenatal
diagnosis. During the course of the project a simple one page high-risk proforma
was designed to be used by the nurses in out-patient department (OPD). Any
patient which has a ‘High risk’ history could be identified. These were given to
the nurses in the OPD to be used at registration. A total of 2965 patients were
registered between 16-38 weeks. Using our proforma in 1996, 45 patients were
identified to be “At risk” for various reasons listed below. In conclusion, we
have initiate a genetic screening programme at a district hospital with a view
to introduce genetic services. The introduction of a specific proforma could be
incorporated at registration. The laboratory did not have the infrastructure to
carry out special tests. The laboratory required strengthening.
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