great read! Didn't get too bored or overwhelmed with information. Also found the book to read very easy rather than anactual scientific article would which made it all that much more enjoyable!

I was unable to read the entire book. I thought it was something different than what it ultimately was.
The topic is interesting but a little too specific for someone with no connection to the field or having encountered any one with the mutation.
I learnt something new from the first couple of chapters and the rest seemed a little too complex for me to follow easily. Not in scientific terminology (which was explained well) but in the direction the author was going.
I think people will better appreciate it if they knew or wanted to know about fragile x

Many genetic disorders follow typical Mendelian genetics—where a person affected by the disease requires two copies of the mutated gene in order to display the disorder, and carriers are those with a single mutated gene displaying no signs or symptoms. However, Fragile X syndrome, a disorder that is caused by variants in genes on the X chromosome and that is the most common single-gene cause of autism, may also cause associated conditions in carriers.

In The Carriers: What the Fragile X Gene Reveals About Family, Heredity, and Scientific Discovery, Anne Skomorowsky, a psychiatrist and clinical instructor, focuses on the premutation carriers, specifically the mothers of Fragile X syndrome children and their family history. She provides a thorough look into the history of medical knowledge and the family lineage of the carriers of Fragile X syndrome, as well as the socio-economic situations and associated disorders that are seen in carriers.

Skomorowsky offers a glimpse into the lives of those living with Fragile X syndrome. She weaves personal accounts into the book along with biomedical evidence and history to create an informative narrative that highlights how little is known about this genetic disorder. However, the writing style may be better for those who have a background and education in biomolecular, genetic, or medical sciences, or a family who is affected by the mutation and would like a further view into the lives of others who are affected.

Still, the writing should not be classified into a scientific reference piece and when reading should be looked at as familial case studies and a single viewpoint on the subject. It is more of a narrative approach that gives insight on family heritage rather than a complete guide to understanding all that is associated with Fragile X syndrome and its carriers. The Carriers: What the Fragile X Gene Reveals About Family, Heredity, and Scientific Discovery is a niche book that currently fills a void in the literature surrounding this syndrome, and it should be considered a stepping stone on the path to learning more.

Thank you, NetGalley and Columbia University Press, for the complimentary copy in exchange for an honest review.

I have a lot of knowledge, personally, with genetic carriers. And this book hit really close to home -- it was once thought that a person in my family would be diagnosed with Fragile X, the carrier trait that is described in this book.

As much as I loved the idea of studying genetics, the topic was just too close to home and I was unable to finish the book.

I received an eARC of "The Carriers: What the Fragile X Gene Reveals about Family, Heredity, and Scientific Discovery" by Anne Skomorowsky from the publisher Columbia University Press via Netgalley in exchange for an honest review.
...

Anyone who’s been gripped by the title of the book or its description would find it a delightful read, especially those interested in the biomedical sciences. The book is tightly wrapped around stories, human stories, which makes it a great read-for-leisure publication. This is because I don’t believe the author meant for the book to be used as a scientific reference. Its purpose: shedding light on an otherwise obscure genetic disorder.

It’s a great book that introduces a rather peculiar syndrome to the average reader. An intriguing genetic disorder with captivating accounts from the people affected by it, and the journey of its scientific discovery.
...

Read the full 7-minute-read review at mustafaabbass.com

#books #bookreview #netgalley #genetics #science #storytelling #mustafaabbass

Thank you NetGaley, who for offering me a free advanced reader’s copy in exchange for an honest review.

Fragile X syndrome is a debilitating poorly-understood disease plaguing multigenerational families, with symptoms increasing in severity from generation to generation. Fragile X syndrome is caused by the repeat of 3 letters—CGG—in the DNA upstream of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene. This gene codes for FMRP (standing for Fragile X Mental Retardation Protein) which is important for brain development, and many other things. In non-affected individuals, the CGG triplet repeats 4-45 times. Affected individuals have more than 200 CGG repeats. In-between, individuals carrying ~50-200 repeats have what is called a premutation; they are assumed ‘healthy’ but carry the risk of having a child with full fragile X mutation in a single generation.

The book discusses the now accepted fact that ‘carriers’ are not just individuals waiting for a silent genetic bomb to go off in their offspring, but experience pathology themselves. The author then details three main syndromes associates with the carrier fragile X status:
1) Fragile X-associated primary ovarian insufficiency (FXPOI)
2) Fragile X-associated tremor/ataxia syndrome (FXTAS)
3) Fragile X-associated neuropsychiatric disorders (FXAND)

Dr. Anne Skomorowsky, who is the author and a psychiatrist, attempted to give premutation carriers a history of how premutation associated syndromes have been discovered, and also offer some life advice. Unfortunately, the book is disorganized, confusing and includes pseudoscientific information and opinions that could be damaging to the individuals afflicted. In my opinion, if you are a premutation carrier and need more information, you should start with Wikipedia. I don’t recommend this book, and I don’t think a lay person is served well, but it may be a stopping point for some. Sadly, there isn’t a lot of literature on the topic available at the moment, so I understand if this may be a starting point for you.

Quick sidenote on the reviewer: I’m a PhD in biochemistry and I also hold a masters in biochemistry and molecular biology. During my masters I worked on a project in another syndrome very similar to Fragile X—namely myotonic dystrophy 1 (MD1). I am very familiar with genetic mutations in which a DNA trinucleotide repeat ‘stutters’, amplifies, becomes silenced by epigenetic mechanisms and also affects RNA metabolism. That being said: I could not understand the mechanism of the disease from the book. I only understood the currently proposed mechanism after reading other publications, because the author made it very very confusing. If a biologist with experience in a very similar field could not follow the explanations, I doubt a lay reader can understand what the author was trying to explain.

However, the book still had the opportunity to offer a voice to premutation carriers and their families including members with full fragile X syndrome. Here too, however, I got lost. The author traveled across the US and even outside the US to Colombia to interview families afflicted by premutation and the full fragile X mutation. Sadly, it was all a blur of extraneous information, not organized in a concise, easy to follow manner. We jump around from interviewer to interviewee, to patient, to scientist, to nurse, to secretary. We are told small stories, the words accumulate, as does the confusion. So much irrelevant information was presented that I have a hard time remembering it and understanding its relevance. I’m again speaking from the perspective of a specialist—as I now transitioned from a scientific career, to one as a medical writer. Clarity is key and clarity was scarce in the ARC I reviewed.

I wanted very much to give this book a high rating, as it had the potential to offer afflicted families a voice. Like one of the scientists in the book says “…if clinicians will really listen to their patients, it is amazing what can be discovered”. And since FXPOI affects women, who as we well know are more likely to have their symptoms overlooked by medical professionals, we are touching on the very important topic of patient self-advocacy in a hostile medical environment. Many gynecologists with whom the author had spoken weren’t even aware the diagnosis of FXPOI existed, even though it has been established more than three decades ago.

The speculations the author put forth however were often superficial and could potentially limit the understanding of lay readers to comprehend how to respond and how to prepare for a carrier status.
Take for example this paragraph on the mechanism of action for Fragile X included in the chapter discussing FXTAS. The author discusses inclusion bodies—which are clumps of protein and RNA accumulating inside a cell like garbage left uncollected in a neighborhood. The author mentions similar inclusion bodies are observed in other diseases where 3 DNA letters ‘stutter’ and are amplified out of control (including Huntington’s disease, or myotonic dystrophy 1); then she continues by saying “Why they [the inclusions bodies] are there [inside the cell] is unclear, but their presence is a sign that the cell is in trouble.” First of all, the inclusion bodies in Huntington and MD1 are VERY different in nature. In Huntington we see a clumping of the mutated protein huntingtin, because the mutation causes the protein to fold incorrectly and to stick together with more mutated, misfolded proteins; this happens in the cytoplasm, meaning outside of the nucleus of the cell. When the cells accumulate a lot of misfolded proteins they are more likely to commit suicide. In MD1, the inclusion bodies occur in the nucleus and they are formed by RNA-protein clumps; in MD1 the mutation occurs outside the region of the gene that would make a protein, more specifically in a region (called intron) that is copied when the gene is read, but is then edited out. The MD1 mutated RNA however ends up forming clumps inside the nucleus which trap proteins meant to edit the messenger RNA (the famous mRNA) into its adult form capable of making proteins. The RNA-protein clumps then completely derail the machine meant to edit mRNA inside the cell. Two very different mechanisms which the author wrapped up with the same vague language "the cell is in trouble". The scientists are not clueless, as the author suggest, about the potential significance of these inclusion bodies. As a lay reader I may as well assume that we’re just divining what’s going on in the cell, and that little is known. Much is unknown in fragile X, but much is known as well. And the author chose the wrong big enigma to represent.

I’ve mentioned also examples where the author could cause harm to the readers. Here are some glaring examples:

1) In chapter 7 we are discussing the case of Carol, a premutation carrier and her family. Carol “had a cancer recurrence. Carol believes in the mind-body connection. She thought positively and used imagery and prayer. Remarkably, her cancer disappeared.” This is a very dangerous statement to make without a cautionary sentence or paragraph about the fact that a) while cancer can spontaneously progress there is ZERO evidence that imagery/prayer has anything to do with cancer disappearance (you can argue it improves hope and quality of life) and b) women have fallen for such approaches AND DIED!! I have not seen the author make this statement in the ARC. Keep in mind that some people who were inside the Chernobyl Nuclear Power Plant when it exploded survived and never got cancer. That does NOT mean we should tell people that it's okay to expose themselves to radiation and that they won't die. Some people are lucky and have good genes, and I expect an MD author to make it very clear that alternative treatments are to be considered thoughtfully. The way this was phrased (and the way other sentences were phrased later on) it sounded like the author may be endorsing such alternative practices as therapeutic on their own. Not a good idea.

2) The author lets multiple experts discuss at large how they believe premutation carriers should abort their carrier children!! I’m pro-choice, and arguments for abortion should be based on logic and good science. In other words: make an informed choice, not one based on fear mongering and misinformation. Later, at the end of the book, the author acknowledges that especially in females, it is hard to predict which X chromosome will become inactivated in the brain cells, thereby suggesting (correctly) that it is impossible to predict if a female premutation carrier will have any significant symptoms, if any! Why wasn’t this discussed next to the advice to abort premutation babies?!? Why was abortion so casually mentioned? Are we now saying that unless the child has NO disability, their life is not worth it? That’s the ableist message I got. Keep in mind, the symptoms one expert thought would be incompatible with life in a premutation carrier included: early menopause and infertility, pain syndromes such as fibromyalgia and migraines, neurological degeneration later in life. How many people live long productive lives with one or multiple of those conditions?

3) The discussion on genetic testing for the children of confirmed carriers was a hot ethical and moral mess.

4) There was a GIGANTIC MESS in the sub-chapter titled “Too Few CGGs is no Safeguard” where the author talks about the dangers of having too few repeats in the DNA preceding the FMR1 gene: “The authors noted that(…)low CGG numbers might increase the survival of embryos carrying BRCA1 and BRCA2 mutations, allowing them to live long enough to develop cancer.” BRCA1 and BRCA2 mutations PREDISPOSE to a series of cancers, including breast, ovarian, prostate and pancreas, THEY ARE NOT LETHAL MUTATIONS!!!!! An embryo with mutated BRCA1 and 2 won't die because of these mutations. The sentence isn’t taken out of context, it’s not in context at all.

5) This statement from the same page, dropped out of nowhere too: “Older women with low repeat numbers were six times as likely to need more drinks to get as tipsy as they had in their youth.” So is the author trying to say that fewer repeats impacts liver metabolism? And only later in life? Perhaps the author should have also considered the very well-known fact that phase 1 liver metabolism changes with age, it usually slows down and could explain the tipsiness changes. Why was this sentence presented then?

6) The book induces non-specific anxiety because of the way the information is not clearly organized and proper disclosures on knowledge limitations are not presented. At one point everything under the sun is linked by the author to premutation carrier syndrome, including type 2 diabetes, but the connection is never explained. (side note: the author succumbed to this anxiety and believed she may be a carrier herself. A test revealed she was not. Now I worry about all those women who are also freaked out by this book and will spend a lot of money on a test they don’t need).

7) In the subchapter “A Confluence of Influences” the author discusses parental distress and maternal depression. A specialist is then cited saying they believe the child’s disease causes the mother’s depression. This whole sub-chapter is very triggering, at times feels like it’s blaming the children and was treated with poor regard for sensitivity. It gets worse later when we’re told that women may be choosing partners who are like themselves (i.e. having mental problems). Again, what happened to sensitivity here? Also, I read very conflicting reports about choosing life partners, with a lot of articles suggesting it's more likely we choose either a mate that a) matches what we've seen at home or b) a mate that has a different but complementary temperament to ours (it's the reason why you often see successful introvert-extrovert pairs).

8) Quote: “Premutation carriers should (…) AVOID EXPOSURE TO TOXINS.” This is a pseudoscientific statement that snake-oil salesmen will love. It is IRRESPONSIBLE that an MD wrote this. Nobody eats toxins willingly. This is fearmongering.

I’m giving the book 2 stars because it may be filling a niche in need of more literature. But this niche needs a better book, and it needs it now.

The truth is that, with few exceptions, I'm generally turned off by the thought of non-fiction. I'm a fan of fictional stories, and I think I've always felt that non-fiction will be dry, boring and difficult to get through. Especially a book about science, cells and medicine when I'm more of a humanities/social sciences kinda girl.
But this book... it's just so interesting. It's written in a very easy, journalistic style and places the author into the story (some people didn't like this, but I thought it felt like you were going along for the journey). It's all the interesting bits of science, full of eye-opening and shocking discoveries, but it's also about history, sociology and race.

I loved this book. Dr. Skomorowsky tells touching stories about people affected by Fragile X disorders. She is an excellent story-teller. Some of the stories are heart-breaking, but needed to be told. Dr. Skomorowsky uses a great deal of compassion in telling these stories, incorporating her own journey along the way. She also explains the science very well and with a conversational tone. Genetics can be so very complicated, but the book provides an amazing amount of clarity. I knew nothing about Fragile X and this book taught me so much. Thank you to Dr. Skomorowsky for providing me with this information and to Netgalley and Columbia University Press for the advance reader copy.

The term “fragile X” comes from the appearance of the X chromosome under a microscope looks broken at the tip or “fragile.”

The genetic disorder fragile X syndrome (also termed Martin-Bell syndrome or marker X syndrome) is the most commonly inherited form of developmental and intellectual disability.

According to the National Fragile X Foundation, “The agreed upon prevalence of FXS in males is approximately 1 in 7,000 and in females 1 in 11,000.” Fragile X syndrome has been found in all major ethnic groups and races.

Author Anne Skomorowsky introduces the reader to several families who have children with the full fragile X mutation as well as the parents and sometimes, the grandparents who are also affected by associated fragile X syndromes. Because the science of fragile X gene is a rather complex subject (and beyond the scope of this review), anyone who is interested in the subject can access the National Fragile X Foundation’s excellent resources at fragilex.org.

I wasn’t familiar with the history of fragile X and the author does an excellent job of recounting the years of research into the affliction.

Anyone interested in the subject will find this book a fascinating read as well as those readers who are more familiar with medical history or mental disabilities would still find it a worthwhile read.

The Carriers: What the Fragile X Gene Reveals about Family, Heredity, and Scientific Discovery by Anne Skomorowsky is a fascinating book that investigates Fragile X Syndrome, a common but relatively unknown genetic condition.

This book is very well written, and very informative. We not only follow scientists on their quest to find out more about Fragile X Syndrome, but we also follow families and societies, and the impact Fragile X has on their daily lives, which is a very interesting approach in my opinion.

The book also explained why Fragile X Syndrome does not follow Mendel's laws of inheritance, and why some carriers are affected, though in different ways than their "fully" affected counterparts.

I would recommend the reader to have at least a basic knowledge of genetics and how gene transmission works across generations, but it is my belief anyone could read this book if they were willing to do some research, since the author has a way of explaining things quite simply.

Overall, an awesome book. A must read for anyone interested in genetics or Fragile X Syndrome.

Looking forward to this book being published. I have spoken to so many people about it because I find it important and educational, we need to be talking more about the Fragile X gene and malformations of the X gene and how that can affect a carrier's life. This was a personal read for me and I wish I had this book before I became a mother. The importance of the medical community to know about this book is extremely important, I was not given genetic testing, and the questions I was asked to see whether I qualified or should take genetic questions did not even come close to the questions brought up in The Carriers. Anne Skomorowsky has given me peace of mind, and the tools to advocate for myself and the rest of my family, I am grateful I was able to read and review The Carriers.

Solid writing and good storytelling, bringing together lots of elements at play in a complex genetic disorder. The author does a great job conveying the nuance and controversy of different doctors and scientists at work in the field of Fragile X. I think this book is for two groups of people: 1. Doctors/scientists who might not be as aware of new discoveries in Fragile X research. I am a pediatrician and certainly learned a LOT. 2. People outside the med community with relatives with Fragile X or new diagnoses of Fragile X in their family, who might seek to think through how this could affect their living and future offspring and families.

My one quibble with the author, and why I couldn't quite give this five stars, is that I felt occasionally her physical descriptions of people in her story were unnecessary, particularly of women, and did not add to her narrative significantly. It would be one thing if she was describing physical traits of the Fragile X disorder, but this wasn't the case. She describes the main doctor on whom her story rests as "the rugged bony daughter of a Norwegian sea captain." Another woman is described as " still [looking] too young to be the mother of a 12 year old." I found this odd for a storyteller who is clearly invested in making sure that the contributions of women to this story are honored--sometimes the physical traits were described first rather than more important attributes.

This book has too much biography and too little science for my tastes. The biography portion is boring while the science portion is quite interesting..