Curse of The Garcias and Role of Sex Chromosomes Discussion An early medical description of a condition similar to androgen insensitivity appeared in a Ger

Curse of The Garcias and Role of Sex Chromosomes Discussion An early medical description of a condition similar to androgen insensitivity appeared in a German journal in 1817. The role of sex chromosomes in the syndrome was not discovered until 1937. The incidence of androgen insensitivity is roughly one in 50,000. l T-Mobile
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second. In Mexico, girls are treated like royalty when they get
their period. But those of us who aren’t able to have children
are treated like slaves. We are forced to serve the others, to care
for them, cook and clean for them. We can’t marry. And then,
when we become too old to work, we’re banished from the
houses of our relatives.”
“Is that why your family came to New Your?” I asked.
“Yes. My parents wanted to do anything they could to
make sure that we wouldn’t end up that way. So they gave up
everything to move here. Still, they don’t want us to talk to
doctors. But I’ve learned in biology class about hormones. I’ve
been thinking this may be an endocrine imbalance.”
“Before we can talk about helping you, we have to figure
out exactly what’s wrong.” I responded. “It’s certainly possible
we’ll find out you have a simple problem that can be treated
with hormones or some other medication. But it it’s also
possible we’ll find a condition we can’t fix. Are you willing to
go ahead, knowing that we may wind up taking away the hope
you have now?”
Imelda considered my question for a few moments before
answering. “You’re right that I have some hope now. But I
want to find out, even if it means I have to accept the fact that
nothing can be done to help me.”
“All right,” I replied. “Let me tell you what we’re going to
do. First, I’m going to examine you. Then I’m going to take
blood for some tests. Those tests may tell us the diagnosis.
When we get the test results, we’ll talk about what can or
cannot be done.
Ellen and I left the room. I asked her what she thought the
problem might be. Without hesitation, she replied: “Androgen
insensitivity syndrome.” I agreed.
In Human Development, being female is, to use computer
terminology, the default. Unless it receives other signals, the
embryonic tissue that gives rise to the external genitalia will
from itself into normal female structures during the first
trimester. Making a male is more complex. A gene called SRY
on the Y chromosome must prompt the undifferentiated
embryonic gonad to become a testis during the seventh week
after conception. That testis must then produce testosterone,
one of a class of male hormones called androgens. Next.
Testosterone molecules must attach themselves to the surface
of the individual cells that form the embryonic sex ducts, the
structures that ultimately give rise to the external genitalia. If
these cells can recognize testosterone, male development
proceeds by prompting the female-forming structures, known
as the Mullerian ducts, to degenerate and the male-forming
structures, called Wolffian ducts, to differentiate into the organs
and ducts needed for male development. Any irregularity in
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Curse of the Garcias
Discover Dec. 2000
Why are so many women in this family unable to conceive?
An early medical description of a condition similar to
androgen insensitivity appeared in a German journal in
1817. The role of sex chromosomes in the syndrome was not
discovered until 1937. The incidence of androgen
insensitivity is roughly one in 50,000.
Two facts about Imelda Garcia struck me when Ellen, our
genetics counselor, introduced her. First, she seemed unusually
nervous. Her hands were balled tightly into fists and her lips
were clenched. Second, she was strikingly attractive, with a
tall, well-proportioned body, pretty face, and long, dark hair.
“you seem nervous,” I began, thinking that an obvious
statement might put her more at ease. She was silent for a
moment. I tried again. “What’s the matter?”
“I’m supposed to be at school now,” she answered. “And if my
parents knew I was here, they would be very angry.”
“Why would they be angry?” Ellen asked.
“They say, There’s nothing wrong with you. They say, God
made me this way and nothing cam be done to change that. But
I don’t believe that. What kind of a God would do that?”
“In the town where I was born, a lot of women have the same
problem as I do. They call it “The Curse of the Garcias’
because so many in my mother’s family have it. Although all
of us look and act like everyone else, we are very, very
different.”
“In what way?” Ellen asked.
“None of us can bear children. We never even get out period.’
As Imelda began telling her story, Ellen recorded the
family history. Imelda was the seventh of eight children, and
she had lived on a small farm in Mexico until her parents
moved the family to New York City five years ago. Two of her
older sisters, she said, were also affected. The problem
stretched back at least four generations: Three of her mother’s
four sisters had the condition. Over four generations, I counted
a total of 16 childless women. That pattern was already
suggesting that the syndrome was linked somehow to a
problem on the X chromosome.
“My mother says she can tell from the time a girl is 4 or 5
whether she is cursed or not,” added Imelda, “but it isn’t until
we are teenagers that things begin to change.”
“How does she know?” I interrupted.
“She says we are prettier than the other girls. But I know
that if I could trade being pretty for being normal, I’d do it in a
second. In Mexico, girls are treated like royalty when they get
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and ducts needed for male development. Any irregularity in
this pathway will lead to either incomplete male development
or the production of an externally “normal looking” female.
In individuals affected with androgen insensitivity
syndrome, also known as “testicular feminization,” the first
three steps occur normally – individuals inherit an X and a Y
chromosome, the SRY gene on the Y chromosome signals the
undifferentiated gonads to form into testes, and the testes
produce normal amounts of testosterone. But then, because of
an error in a gene carried on the X chromosome, the cells that
are supposed to bind testosterone to their surface and initiate
male development can’t recognize it. So, in spite, of carrying a
Y chromosome and making lots of testosterone, these
individuals develop into women who have testes in their
abdomen instead of ovaries, Because the male-making effects
of testosterone are tharted, the body converts the hormone to
estrogen, so these women tend to develop full figures. Overall,
they are perfectly healthy, but the testes can, in rare cases, turn
cancerous, so they’re usually removed when the patient
completes development. At that point, the patient must begin
estrogen replacement to avoid entering menopause.
Imelda’s exam showed she was not normal in two ways.
There was no axillary or pubic hair, and her vagina was very
short, ending in a blind pouch. Given her exam and the
abundance of affected women in her family history, I was
nearly certain that the Garcias’ problem resulted from inherited
S-linked androgen insensitivity syndrome. But I would need a
blood test to confirm the diagnosis. The test indeed showed
that Imelda had one X and one Y chromosome in her cells. And
her hormone testing showed an extraordinarily high level of
testosterone. Her endocrine system was screaming for her body
to make a man, but her cells were deaf to those instructions.
Before Imelda returned to discuss the tests, Ellen and I
had decided to let Imelda start with her own questions. We
agreed that we wouldn’t tell Imelda about the results of the
genetic test unless she brought it up. Telling a woman she has
the chromosome complement of a man can have long-term and
far-reaching psychological consequences.
When Imelda arrived, I started by saying, “The tests
showed that you have an alteration in one of your genes. This
gene is responsible for causing your internal structures to
mature.’
“Does that mean something is wrong with the gene that
causes estrogen to be made?” Imelda asked.
“Not exactly,” I replied. “It’s the gene that causes the cells
of the body to be able to recognize the presence of the sex
hormones. Because of the way the gene is altered, your internal
structures are unable to recognize hormones. As a result, they
did not develop as they should have, and when you’re a few
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The Curse of the Garcias – Androgen Insensitivity
Question Sheet
1.
What aspect of Imelda’s family history was unusual?
2.
Which of Imelda’s chromosomes carries the mutant gene?
3. Did Imelda receive her mutant gene from her mother or
her father?
4. Where is the SRY gene located and what does it do? (On
which chromosome number )
5.
Does Imelda have a mutated SRY gene?
6. What happens if a developing fetus doesn’t receive an
SRY gene?
7. Does Imelda produce the male sex hormone,
testosterone?
8. Why didn’t the testosterone trigger the development of
male characteristics when Imelda was a fetus?
9.
What happens to the testosterone that Imelda produces?
10. If you were the doctor in this article, would you have
given Imelda all the details?
11. If you were Imelda, would you have wanted all the
details?
12. What do you think; Is Imelda a man or a woman?
13. If a technique were available to correct this mutation,
would you support its use if …… ?
• The developing embryo could be tested for the mutant
chromosome and it could be swapped for a normal
chromosome.
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Tuy
did not develop as they should have, and when you’re a few
years older, you’ll need an operation to remove your gonads.”
“Does this mean my womb didn’t develop?” Imelda
asked.
I nodded
“You mean I can’t have children?”
Her eyes filled with tears.
“Imelda, I wish we’d found something that would bet
better with medication. I ‘m sorry.”
“This doesn’t make you any less of a person,” Ellen said.
“You’re not in Mexico now, you’re in New York. And in New
York, women who can’t have children aren’t considered
useless, hopeless people. You’re young, you’re smart, and you
have your whole life ahead. You can be anything you want to
be”
“Except a mother,” Imelda added.
“It is true that because of this problem you won’t be able
to bear children of your own,” I said. “But you can always
adopt children. And being a mother to an adopted child is just
as satisfying as being a mother to a child you’ve borne
yourself.”
There was silence in the room for a few seconds. “When I
cam e here last week,” Imelda finally said, “you asked if I
wanted to go ahead with this, even though there was a chance
I’d find out that nothing could be done. Even though it worked
out this way, I think I made the right decision.”
I was glad she felt that way, but I found this a frustrating
message to deliver. In recent years, thanks to the genetic
revolution, physicians can discover detailed answers to
complex diagnostic questions that used to remain mysteries.
But the ans vers don’t necessarily make anything better. In one
way or another, we all have to live with who our genes have
dictated we are.
The case described in Vital Signs is based on a true story. Some
details have been changed to protect the patient’s privacy.
Robert Marion is a professor of genetics at Albert Einstein
College of Medicine and director of genetics at Montefiore
Medical Center in New York City. Although androgen
insensitivity is relatively rare, Marion says he sees about one
case every five years. Marion’s recent books include Learning
to Play God and Intern’s Blues.
The Curse of the Garcias – Androgen Insensitivity
Question Sheet
1.
What aspect of Imelda’s family history was unusual?

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