Usher syndrome part IV: Clinical management and research directions

Guest Blogger Danio, one last time:

Part I
Part II
Part III

The current standard of pediatric care mandating that all newborns undergo hearing screenings has been applied successfully throughout much of the industrialized world. Early identification of hearing impairments gives valuable lead-time to parents and health care providers during which they can plan medical and educational interventions to improve the child’s development, acquisition of language skills, and general quality of life.

Up to 12% of children born with hearing loss have Usher syndrome. However, diagnosing Usher syndrome as distinct from various forms of congenital hearing impairment is often impossible until the onset of retinal degeneration years later. The considerable number and size of the genes involved makes genetic screening impractical with the current methods, unless there is a family or community history that can shorten the list of targets by implicating a particular Usher gene or subtype.

The educational and medical interventions undertaken to improve a deaf or hearing-impaired child’s cognitive and social development can vary extensively, based in part on whether the child in question is expected to lose his or her vision later in life. Thus an earlier diagnosis of Usher syndrome is an immediate and critical research goal. The most imminent hope for such a diagnostic advance lies in gene chip screening. With this technology, the patient’s DNA can be screened against a microarray of human genes known to cause deafness (and/or Usher syndrome) when mutated, and variances in the DNA sequence of any screened gene would be detected and analyzed. One such chip is already available for commercial use, and another appears to be approaching clinical availability. The rapid and affordable analysis these microarrays offer will be of tremendous benefit in the early diagnosis and management of Usher syndrome.
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Protecting the Right of Conscience?

Guest Blogger Danio, sneaking a few more posts in:

Remember that execrable HHS policy document that proposes an extension of the current protections for health care workers who refuse to provide or assist in treatments that they personally find morally objectionable? I did a little back-tracking on this issue, and followed the trail of HHS Secretary Mike Leavitt, who requested this regulation after a “disappointing” interaction with the American College of Obstetricians and Gynecologists. He has since been unwavering in his support of the proposal–which he claims is not about abortion OR contraception, but about conscience rights–and has a recent blog post responding to the feedback he’s received from pro-choice activists as a result of the leaked document.

Here’s the money quote:

Is the fear here that so many doctors will refuse that it will somehow make it difficult for a woman to get an abortion? That hasn’t happened, but what if it did? Wouldn’t that be an important and legitimate social statement?

“Social statement?” I can scarcely get my mind around the fact that he is so openly, unapologetically endorsing a policy in which pious opinion would trump secular law. Once again, though, it shouldn’t be a surprise. After all, he himself states that “The Bush Administration has consistently supported the unborn”. Ah yes, even as they indiscriminately leech the quality of life (if not the life itself) from countless other self-aware, functioning humans on the planet, each and every blastocyst they encounter is ceremoniously wrapped in a mantle of sanctimonious protection.

Somehow even more disheartening are the numerous fawning, unctuous comments on Leavitt’s recent blog entry. One wrote:

Secretary Leavitt,

It is beyond my comprehension that anyone would be offended by a health care professional who valued human life. But the tragedy is our culture has regressed to a form of barbarism unseen in centuries where progress in technology and science has poisoned our minds, hearts and souls where the intentional destruction of innocent and vulnerable human life has become more important than saving it.

Those of us living and working in a society where human life is expendable by government dictate but fail to stand up to protect and cherish life at any and all costs will live to regret it.

You are doing the right thing Secretary by allowing those of us in the health care profession live our moral and ethical consciences rather than forcing us to choose another profession.

Choose another profession like….a PETA supporter working in a meat packing plant?An auto mechanic who doesn’t support the use of fossil fuels?

Keep your eyes on this one. It has ‘lame duck’s parting shot’ written all over it.
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UPDATE: Leavitt has a new blog entry up today announcing that the proposed rule is being filed in the Federal Register. Although the final draft no longer contains the specific language broadening the definition of “abortion” to include anything from “conception” onward, it still threatens to withhold Federal money if health care organizations don’t allow their employees to exercise their rights of conscience.

Usher syndrome, part III: the plot thickens

Guest Blogger Danio:

The time has come to delve into the retinal component of Usher syndrome. In Part II, I briefly described the results of protein localization studies, in which most members of the Usher cohort were found at the connecting cilium of the photoreceptor and at the photoreceptor synapse. The following diagram summarizes these findings:

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Usher protein localization in photoreceptor cells. From Reiners, et al. 2006

So, as we saw in the ear, proteins with the equipment for physically interacting with one another are gathering in specific places, and thus multi-protein complexes are likely being formed at these locations. The cluster of Usher proteins around the connecting cilium has been the focus of most of the current retinal studies, and to understand the potential importance of an Usher complex at that subcellular location we must address the importance of the connecting cilium itself.
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Another poll for your Monday morning… Canadian style

Canoe’s recent poll asks: Do you believe physicians should have the right to refuse medical treatment if it is against their beliefs? Scroll down to the bottom of the right hand side of the page to find the poll.

To clarify, as it’s been brought up that this is a poorly worded poll: based on the story behind it, it is referring to doctors who refuse their patients medical treatment that will help them based on their religious beliefs.

But nevermind anyways. Apparently this poll was closed just after I posted it. So ignore the link, but feel free to comment on the topic if you like.

Now luckily common sense is already winning out with 61% of the ~2300 voters voting no. However, that still leaves close to 40% of voters who believe this practice is OK. Let’s get to work!

This poll brings up a good point of discussion, I think. I personally have heard of many stories of, for instance, unmarried women having to find a new family doctor because they wouldn’t prescribe her birth control, due to the doctor’s religious beliefs. Obviously, I think this situation is beyond ridiculous.

From LisaJ.

“Brainwashed” by god into killing her child

LisaJ here again.

Wow. Now here’s a story that just disturbed me to no end. Little Javon Thompson’s mother, 21 year old Ria Ramkissoon, became a Christian at a young age, but when her local pastor disappointed her by pleading guilty to molesting young boys, she left her church and was taken in instead by what is now being described as a dangerous religious cult (I’d like to make the point that even plain ‘ole regular Christianity is a dangerous cult, but that’s beside the point). This cult, called 1 Mind Ministries, is headed by a 40 year old, I’m assuming woman, who calls herself Queen Antoinette, and it appears that the relatively small group lives together and operates under the extremely god-driven Queen’s direction.

What happened to Javon, Ms. Ramkissoon’s little boy, in 2005 is what has me so disturbed. The ONE year old child was denied food and water for two days because he wouldn’t say “Amen” after finishing his meals. This outrageous punishment killed him, and none of his caretakers intervened to save him. Police say that the group viewed this child as a demon, and that they left his lifeless body in a backroom of their apartment for more than a week while they simply prayed to god to raise Javon from the dead. Instead, the boy’s body began to decompose and no resurrection occurred, obviously.

Reportedly, after the cult members accepted that Javon would not be resurrected they stuffed his body in a suitcase. His mother lovingly added mothballs and fabric softener to the contents of the suitcase, and occasionally sprayed some disinfectant inside. The case, with the child’s body still inside, was found earlier this year, after it had been stored behind a home in Philadelphia when the cult relocated to New York City, over a year earlier.

Javon’s mother Ria and four other cult members face first degree murder charges in this case. Ria’s mother, however, contests that her daughter was brainwashed by the cult. Her attorney has recently declared that “the members of this cult, who were more than twice her age, were calling the shots,” and that “she bought the program hook, line and sinker.” So because this young woman was reportedly brainwashed, does this then mean that she should not be prosecuted with her child’s murder? To put this into perspective for myself, I was raised catholic, and there are certainly many faulty decisions I made while growing up that I consider to largely be the fault of my indoctrinated mindset. But murder? I have a really hard time swallowing the brainwashing excuse as justifying your active involvement in your child’s murder. And besides, even if her supposed brainwashing is really at fault here, someone this stupid to allow someone to talk her into effectively killing her child, under the guise of god, should be put away where she is no longer a danger to herself or anyone else.

This disturbing story highlights perfectly the dangers that society faces for teaching people to believe in whatever god they’re confronted with, instead of thinking for themselves.

A problem with normal

MAJeff here.

LisaJ’s Danio’s (hangover error) posts about Usher Disease (I and II), as well as my own syllabus preparation for the upcoming semester, have gotten me thinking about issues of intersexuality. In particular, her noting of the geographic issues related to the prevalence of various forms of Usher disease reminded me of the concentration of five-alpha-reductase deficiency in parts of Turkey, Papua New Guinea and the Dominican Republic.

Some folks are probably asking, “What is this intersexuality thing?” Basically, it’s a range sexual development disorders in which people’s bodies develop in such a way as to place them in a “border region” of sex. Hermaphrodism is what people usually think of, but there is a wider range of conditions, including hypospadias and congenital adrenal hyperplasia.

If any of you have read the novel Middesex you already have an idea of what I’m talking about with five-alpha-reductase deficiency. People with this condition are genetically XY, but during fetal development something happens such that in many people the testicles may not descend, the scrotal sac may not fuse, and the penis can appear more like a clitoris (such an ambiguous thing is often called a microphallus). Because of these developmental issues, people with this condition are given a female gender designation at birth. Once puberty hits, though, the testicles descend, the penis may enlarge, the “labia” fuse to form a scrotum, and other male secondary sex characteristics appear. One of the things I find so interesting about this particular condition is the way that it has been routinized in the patterns of life and cultural systems in parts of the Dominican Republic. The people living in these areas have their own term for the condition, “guevedoce” (“eggs/balls at 12”).

In class, I often use a video produced by the Intersex Society of North America, an organization that shut its doors this years in favor of a different advocacy organization, the Accord Alliance. In particular, this segment of that video talks about, and interviews, someone who identifies as a guevedoce, as well as his family. (YouTube won’t allow it to be embedded.)

It’s this issue of how people with various conditions are integrated into social life that is my primary concerns. One of the things intersex activists have been challenging for the past decade or so is infant genital surgery. When children with some sexual development disorders are born with ambiguous genitals they are quite literally made to fit into one of the existing gender categories. “Fixing” them means surgery to make their genitalia more closely resemble “normal” genitals. If the phallus falls inside the middle range, where it’s “too long” for a clitoris or “too short” to be a penis, well, it’s snip-snip time. Many of the decisions to engage in surgery are based not on medical necessity, but social preference. Questions such as, “Will he be able to stand to urinate?” or “Will her partners be turned off by such a large clitoris?” or “How will the parents deal with looking at such a strange body while changing diapers?” can become more important issues when determining whether to operate than such things as “Will cutting part of the phallus off affect this child’s sexuality later in life?” (Ann Fausto-Sterling has an excellent discussion of these issues.)

Not surprisingly, surgeries do affect folks. Many report a loss of sensitivity from having such operations performed on them. (As one of my students once said to the other women in the class about the possibility of having half a clitoris and no sensitivity, “Wouldn’t it just make you tense all the time!”) It’s more than loss of sensitivity, though. There are often other complications that require more than one surgery. Ongoing pain or recurrent infections are not uncommon.

This is one of those spaces where I get all anti-normalization. These people’s bodies are being normalized–they are being reconstructed so they fit within normative assumptions about what genitalia must look like based on statistical averages. And, it’s done without their consent. Intersex activists have been successful in increasing awareness in the medical profession, but there are still issues. Many of these flow from the gender order we have in this society. The problem with such medically unnecessary genital surgeries isn’t these babies’ bodies, but social beliefs about what those bodies are supposed to look like.

My connection to Sonic Hedgehog

Some more pure science from guest blogger LisaJ:

Everyone seems to love a little Sonic Hedgehog around here. Whenever PZ discusses another function that this fascinating gene is capable of, much excitement ensues in the comment posts. So I thought I would take this opportunity to talk a bit about what I study, and how my seemingly unrelated favourite protein pathway is also connected to the Shh gene.

The main protein that I study was originally identified through studies of a pediatric eye cancer, called Retinoblastoma, as loss of function of this protein (termed the Retinoblastoma protein, or pRb for short) was found to be causative in the formation of this tumour type. What we know now is that pRb is required to control normal cell division in all cell types; its functional loss leads to the formation of many types of tumours, and is thought to be involved in the development of at least half of all human cancers. Not only is pRb essential in preventing uncontrolled cell division that can lead to cancer, but it is also essential for embryonic development, as mice deficient for the Rb gene die by about the 15th day of gestation, about 5 days before they would be born.

To explain how pRb functions in the cell, I thought that I could easily pull out a figure from a review paper that diagrams a simplified cell cycle pathway and the protein interactions that take place. But instead, I’m going to show you this beautiful piece of work that a few of my talented previous lab mates created for me one day, as a means of cheering me up after a year’s worth of protein purifications and binding assays did not give me the result I was hoping for. Although a simplistic depiction of cell cycle regulation, I think it really drives home the point well of how pRb functions.

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In which Danio assiduously avoids all mention of consecrated wafers

Johann Hari had a great piece in the Independent this week (with follow-up blog posts here and here) about increasing scrutiny of religion in general, and of Islam in particular.

An author named Sherry Jones has written a book, called The Jewel of Medina, that will never see the light of day because it novelizes the life and times, with particular focus on the marital details, of the prophet Mohammed.

The Jewel of Medina was bought by Random House and primed to be a best-seller – before a University of Texas teacher saw proofs and declared it “a national security issue”. Random House had visions of a re-run of the Rushdie or the Danish cartoons affairs. Sherry Jones’s publisher has pulped the book. It’s gone.

Hari goes on to criticize the kid gloves with which Islamic issues are dealt the world round, contrasting it to the relative ease with which people question the tenets of Christianity and other more ‘docile’ world religions. Although his East End perspective may not allow him to fully appreciate the rebounding resistence to criticism sought by Christians in America, his general conclusions are spot on:

It is condescending to treat Muslims like excitable children who cannot cope with the probing, mocking treatment we hand out to Christianity, Judaism and Buddhism. It is perfectly consistent to protect Muslims from bigotry while challenging the bigotries and absurdities within their holy texts.

There is now a pincer movement trying to silence critical discussion of Islam. To one side, fanatics threaten to kill you; to the other, critics call you “Islamophobic”. But consistent atheism is not racism. On the contrary: it treats all people as mature adults who can cope with rational questions. When we pulp books out of fear of fundamentalism, we are decapitating the most precious freedom we have.

Naturally, he is receiving a quantity of shrill concern-troll style email for daring to sing a refrain that might sound a bit familiar ’round these parts: NOTHING IS SACRED. The responses of anger and fear are as predictable as they are sad, and just as many, if not more, of the complaints are coming from the uber-tolerant left. It is frustrating how glibly the term ‘bigot’ is now deployed, from a seemingly untouchable ultra-politically correct position. I long as much for the freedom to call ‘bullshit’ when warranted as I do for the day when, through efforts of vocal rationalists and moderates, the chinks in Religion’s armor have been widened enough to let the light stream in, and words and symbolic actions challenging the merits of any faith or philosophy can be spoken, read and conducted with impunity.

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Just in case it’s not clear from the title, this post was authored by Guest Blogger Danio.