The Family Gene: A Mission to Turn My Deadly Inheritance into a Hopeful Future – An Intimate Medical Mystery About Private Mutation and Survival

by Joselin Linder

A riveting medical mystery about a young woman’s quest to uncover the truth about her likely fatal genetic disorder that opens a window onto the exploding field of genomic medicine When Joselin Linder was in her twenties her legs suddenly started to swell. After years of misdiagnoses, doctors discovered a deadly blockage in her liver. Struggling to find  an explanation for her unusual condition, Joselin compared the medical chart of her father—who had died from a mysterious disease, ten years prior—with that of an uncle who had died under similarly strange circumstances. Delving further into the past, she discovered that her great-grandmother had displayed symptoms similar to hers before her death. Clearly, this was more than a fluke.

Setting out to build a more complete picture of the illness that haunted her family, Joselin approached Dr. Christine Seidman, the head of a group of world-class genetic researchers at Harvard Medical School, for help. Dr. Seidman had been working on her family’s case for twenty years and had finally confirmed that fourteen of Joselin’s relatives carried something called a private mutation—meaning that they were the first known people to experience the baffling symptoms of a brand new genetic mutation. Here, Joselin tells the story of their the lives it claimed and the future of genomic medicine with the potential to save those that remain. 

Digging into family records and medical history, conducting interviews with relatives and friends, and reflecting on her own experiences with the Harvard doctor, Joselin pieces together the lineage of this deadly gene to write a gripping and unforgettable exploration of family, history, and love. A compelling chronicle of survival and perseverance, The Family Gene is an important story of a young woman reckoning with her father’s death, her own mortality, and her ethical obligations to herself and those closest to her.

Genres: Nonfiction, Memoir, Science, Medical, Health, Medicine, Biography

272 pages, Paperback

First published March 14, 2017

About the author

Joselin Linder is a regular contributor to the NEW YORK POST, whose work has also been featured on THIS AMERICAN LIFE, MORNING EDITION and LIFE OF THE LAW. She spoke at the TEDX GOWANUS event in Brooklyn in 2014, presenting for the first time on the subject of her family gene and the deadly illness to which it leads. Exclusive to just fourteen people, the story of the gene will be told in Linder’s new book, THE FAMILY GENE, coming out in 2017. She lives in Brooklyn with her husband and two dogs.

Reviews

[Rebecca · Rating 4 out of 5]

(3.5) My eye was drawn to The Family Gene because of the medical mystery aspect: 14 members of Linder’s Ashkenazi Jewish family are the only known exemplars of their particular genetic disease, so rare it doesn’t have a name or surefire treatment protocol, but now at least has a location on a chromosome.

Linder’s awareness of her family’s peculiar medical problems began when her father, William, himself a doctor near their home in Columbus, Ohio, started having a persistent build-up of lymph (also known as chyle) in his abdomen – usually a sign of heart or liver failure. At one point doctors tapped four liters of the stuff from his lungs. Her father’s illness threw Linder, then a junior in college, for a loop; drugs and music started to replace academics. After he died, aged 49, in September 1996, she became a nomad, moving from Prague to San Francisco to Brooklyn and dabbling in different careers.

Only gradually did they all realize that the same thing had happened to William’s uncle, Nathan, in the 1960s and his grandmother, Mae, before that. While Mae lived to age 54, Nathan died at 34, even after treatment at NIH. Along with the lymphedema, a heart murmur was a common factor. William’s brother, Norman; Linder and her older sister, Hilary; and various cousins of their generation were diagnosed in this way. The author’s own symptoms were initially easily to ignore – swollen ankles and a low platelet count – but escalated in her thirties: a blocked vein in her liver meant she was in danger of bleeding out if she vomited.

It’s rare to be able to trace a genetic disease from its founder through to the present. In Linder’s case, her great-great-grandmother, Ester Bloom, is the first known sufferer. Researchers eventually isolated their family’s gene on the X chromosome, near the location for asthma. This explained why, historically, female family members had a better prognosis than males – they have one normal X chromosome and one diseased one; men only get the defective X chromosome – and why asthma medication helped to an extent.

There are a couple of chapters here on the basics of genetics that felt a little condescending to me; for anyone with a high school or A level biology qualification, the simplistic metaphors explaining the workings of DNA may seem superfluous. I also had trouble relating to Linder’s immediate reaction to her father’s death. Although he’d been severely ill for years by then, her attitude still seems a little heartless. Of the decision to take him off dialysis, she writes, “I was on board. It was time to call it a day.” When the family went around expressing opinions, she said, “I think it’s time, Dad. You’ve been through so much,” to which he replied “F— you”! An ex-boyfriend’s suicide a couple years later affected her much more than her own father’s death. Grief affects people in strange and unpredictable ways, I guess.

What I most appreciated was how the book sensitively reveals the ways a genetic condition complicates life, especially in America: Linder had to do without health insurance for 10 years, having been denied it in Ohio on the grounds of a pre-existing condition. In addition, she and her sister faced a quandary common to those who carry genetic diseases: should they have children? While Hilary underwent pre-implantation genetic diagnosis, a form of IVF, to bear healthy twins, Linder ultimately decided against having children.

I enjoyed the earlier part of this genetic quest narrative a bit more than the later material about Linder’s symptoms. Still, I can recommend this to viewers of House and readers of Susannah Cahalan’s Brain on Fire and the like.

Originally published on my blog, Bookish Beck.

[Jessica J. · Rating 4 out of 5]

When Joselin Linder was a teenager in the late 80s, her father grew ill. His symptoms—primarily, that his body was swelling and his lungs were filling with fluid leaking out of his lymphatic system—confounded doctors, as they didn't seem to align with any known condition. There seemed to be no discernible reason for this to be happening to an otherwise healthy, middle-aged man. And there seemed to be no way to treat his symptoms.

But some older relatives recognized the symptoms: they were the same ones that had killed both his grandmother and his uncle in the mid-20th century.

Eventually the Linder family and their doctors began to realize that the condition was tied to genetics: something was wrong with a gene that was being passed through this family and it was causing these symptoms. As far as anyone could tell, just fourteen people in the entire world had this gene—all descended from Joselin’s great-great grandmother—and five had succumbed to the deadly disease that it caused.

By the time that Joselin's father succumbed to his illness in 1996, the medical community's understanding of genetic disorders was growing by leaps and bounds, but there were still huge gaps in the knowledge. As the Human Genome Project neared completion and genetic mapping became a reality, medical experts studying the family began tracing the source of their disease. They were looking for the exact chromosome that carried the faulty gene and trying to figure out exactly what it was doing to the body so that the fatal symptoms could be alleviated. Meanwhile, Joselin and her sister Hillary were struggling to reconcile their desire to start a family with the fear that this faulty gene could be passed on to their own children.

This is a fascinating medical mystery that will appeal to anyone who’s enjoyed books like The Immortal Life of Henrietta Lacks, which Linder herself namechecks in her explanation of genetic science. Though some of the science gets a bit dense—don’t expect me to clearly explain exactly what this disease was doing to the vascular system and the liver, nor exactly how gene mapping works—Linder does a pretty good job distilling it down into layman’s terms. After all, she’s not a scientist and she’s had to figure out what’s going on inside her own body. That being said, the writing could be a bit clunky at times. I was reading an advanced copy, so it’s possible that more editing was done, but I also think that this book came about from some work being done for a public radio piece that was eventually got scrapped. And honestly, at times the sentence structure felt more appropriate for a radio piece than for a book. It’s hard to explain, but the writing styles are (understandably) different between the the two mediums, and it doesn’t always quite gel here.

Still, it’s a book that will make you think. Genetic diseases are absolutely terrifying. Knowing that you are destined to develop a disease and there’s nothing that can be done about it? I can’t even begin to imagine how difficult it must be to process that and carry on in spite of it. The science of genetics is still relatively young and it suffers, to some extent, from public ignorance. There are some people who question the ethics of genetic manipulation, but Linder argues that we need greater understanding of these diseases and their complicated roots. She does an excellent job putting a human face and a human story on what could have easily become dry, clinical science talk.

[CatReader · Rating 4 out of 5]

In The Family Gene, Joselin Linder tells the story of her paternal family's health history, where her father, many members of her extended family, and the author herself have been affected by an unnamed (to the best of my knowledge - couldn't find an entry in OMIM), X-linked genetic disease that is fatal in affected males and has an attenuated but still significant disease presentation in affected females. Linder presumes the reader has no background on genetics or medicine; as someone with good familiarity in both areas, I think she largely did a nice job of explaining relevant concepts.

Her story is poignant, particularly as she talks about losing her father (who was a physician) to this disease in her early 20s, and her decisions regarding childbearing (her sister, who is also affected, goes through IVF with pre-implantation genetic diagnosis to select for unaffected embryos, and she goes on to have twins).

Further reading - books about families with genetic diseases:
Mercies in Disguise: A Story of Hope, a Family's Genetic Destiny, and the Science That Rescued Them by Gina Kolata (Creutzfeldt-Jakob Disease; hereditary)
The Boy Who Loved Too Much: A True Story of Pathological Friendliness by Jennifer Latson (Williams syndrome; genetic but not hereditary)
Raising a Rare Girl: A Memoir by Heather Lanier (Wolf-Hirschhorn syndrome; genetic but not hereditary)

[Joy D · Rating 3 out of 5]

“You should fight to live long and well, you should experience meaningfulness as often as you can, and the rest of the time you should just ignore death completely.” – Joselin Linder, The Family Gene

Non-fiction memoir about a family with a genetic variant. Joselin Linder inherited a unique gene from her father, which causes a currently unnamed disease that has resulted in the deaths of five family members. In this memoir, the author documents her family’s pain and suffering, the genetic research involved in tracing the source, and the medical analysis involved in discovering a treatment. She talks about what it is like living with a potentially fatal condition.

This book covers a good amount of medical science in a manner easily understood by a layperson. It shows how this family turns tragedy into an opportunity to work in partnership with doctors and scientists to understand and reduce the impact of this unique disease. The author intersperses information about the history and recent advances in genetics into her personal story. The writing style is colloquial, with humor sprinkled throughout, as a respite from the weighty topics. Linder only touches the surface of the genetic engineering debate, instead offering her personal insight from a perspective of someone with a significant stake in the outcome.

Recommended to those interested in medically-oriented memoirs, hereditary diseases, and genetic research. I think fans of The Immortal Life of Henrietta Lacks, Brain on Fire, or Lab Girl may also appreciate it.

[Stetson · Rating 5 out of 5]

This is a competently written, moving medical memoir concerning a private (aka unique) genetic variant (aka mutation) co-segregating (aka a variant-disease association across generations) with a mysterious disease - characterized by a heart murmur, swelling in the lower limbs and other body compartments, and eventually an inability to assimilate nutrients - in an Ashkenazi Jewish family from Ohio. The proband (genetics jargon for the reporting patient) is the author's father, who tragically succumbs to the disease despite a valiant fight. The core of the memoir follows Linder's coming-of-age during her father's harrowing decompensation and her own eventual medical odyssey as she traces the history of the mysterious genetic disease in her family.

Linder's father, a physician himself, had a fairly normal medical history (apart from experimental open heart surgery to fix a heart murmur as a child) until, in his late 40s, he developed unexplained swelling and fluid accumulation in his body that required drainage and could not be explained by typical causes. Despite extensive medical evaluations, his condition remained undiagnosed, culminating in his premature death. Her father's case precipitate a re-discovery of similar deadly illnesses in her family's history, stretching all the way back to her great-great-grandmother, Ester Bloom.

Determined to uncover the cause, Linder and her family connected with Dr. Christine "Cricket" Seidman, a cardiovascular genetics expert at Harvard Medical School. As the research developed, it becomes clear that the condition is X-linked yet still affects the female carrier, suggesting dominance effect (XLD), though X-linked inactivation does appear to delay disease onset and moderate symptoms in these female carriers. Eventually, classic linkage analysis identifies promising candidate region on the X chromosome where a gene already associated with asthma risk is located. Sequencing of this region resulted in the discovery of the private variant.

Unfortunately, it doesn't appear that any of this vital genetic information has not been published in scientific journals. Linder herself doesn't explicitly disclose even the gene name let alone the private variant. Talking formally about genetics doesn't make for great reading, but it would have improved the work if some of the more technical information was included in end notes or foot notes or something. I listened to this book so this may be the case, but from what I can tell, it is not. It is also unclear why the Seidman has not published this work, which has clearly been active for decades. It is possible publication has been withheld for reasons of privacy.

Anyway, I found this all a bit mysterious given there is a book for lay audiences available so I tried to look into this a bit. I'm fairly confident the candidate gene is CYSLTR1. This is just based on Linder's description in the book and the location of that gene on the X chromosome. CYSLTR1 encodes a protein called cysteinyl leukotriene receptor 1. It is a G-protein coupled receptor, which is the largest major receptor family in the genome, that binds to cysteinyl leukotrienes (CysLTs), which are inflammatory mediators. Per Linder's description, CYSLTR1 is thought to be critical to the regulation of vascular pressure in portal circulation. Subsequently, the inciting pathophysiological events in many of Linder's relatives, including herself, appears to be catastrophic narrowing or obstruction of the portal vein, which appear related to a change of CYSLTR1 receptor expression in liver vasculature over time. The exact variant responsible for the dysfunction in CYSLTR1 is unknown. I've checked resources like gnomAD and ClinVar for loss-of-function variants and have found few reported or at least few plausible candidates. From Linder's description, it seems possible that the private variant could be a gain-of-function missense variant, a missense variant that affects the stability of CYSLTR1, or even a regulatory variant. It is also unclear why the researchers believe CYSLTR1 is most vulnerable in portal circulation than other organ systems, where cysteinyl leukotriene play an important role in physiology. The SNP in CYSLTR1 associated with asthma risk is the synonymous variant c.927T>C p.Phe309Phe (rs320995). Perhaps there is some relationship to the private Linder variant as their family takes and appears to respond to Singulair (montelukast), as asthma drug, to prevent the portal vein stenosis. The fact that montelukast is a CYSLTR1 antagonist suggest that the causative variant may have a gain-of-function effect, but this conflicts with Linder's description of the patho-mechanism. So we're still left with some mystery.

Although this medical memoir raises some questions it doesn't answer, the picture is filled in enough for lay readers, who will likely find this an engaging, light-hearted though sometimes tear-jerker of a medical detective story and family saga. It is also an economic book that can be breezed through in a single sitting. I recommend.


My extended review of The Family Gene. It covers my rationale for why I think their private founder mutation has a gain-of-function effect and provides a pedigree of the family.

[Barbara (The Bibliophage) · Rating 4 out of 5]

The Family Gene by Joselin Linder is everything I wish for in a medically-oriented memoir. Linder blends the science of genetics deftly with her own family’s story. It was so compelling that I flew through the book in just a day or so.

When Joselin is just fifteen, she and her family begin to watch her father die a slow, painful and frankly horrific death. He literally never received a diagnosis for this fatal disease. The family begins to realize that his condition was very similar to two other members of his family, now also deceased. Then his brother dies. Sounds overwhelmingly sad, doesn’t it?

Full review at http://thebibliophage.com/book-review...

[Marika · Rating 5 out of 5]

A compelling medical mystery that involves a faulty gene that is inherited. The author's legs began to swell when she was in her early 20's and the medical profession was stumped as to the cause. So began Joselin's journey to decipher what is truly going on. She begins by reviewing her father's medical chart (he was a physician) as to what caused his death. This is a true medical detective book that will leave readers cheering and hoping for Joselin and wondering about their relatives that died peculiar deaths.

I read an advance copy and was not compensated.

[Phil · Rating 4 out of 5]

I was pulling into the parking lot of the supermarket where I shop, listening to NPR. The interview with Ms. Linder that was so fascinating, so interesting, I sat in the parking lot until the interview ended. And I promptly ordered the book.

I have a potentially fatal genetic disorder, but at 72 I do not give it much thought. I know of no one in my family history who had it. (But could it have been properly diagnosed?)

Is my case a "one-off," a one time thing? Am I the first documented case in my family? Will any of my descendants develop it?

Ms. Linder's account did not and cannot address mine, but it helped me understand.

I must say, Ms. Linder has a wonderful gift for making complex scientific, medical, and genetic terms comprehensible to this lay-person

My only reluctance to grant five stars is my disinterest in her personal Sturm und Drang during adolescence.

[Diana · Rating 2 out of 5]

I read this book quickly because I skimmed or skipped the essays about genetics, the movie reviews and the book reports. There wasn’t much left. What there was of the author’s story of her family’s genetic mutation was interesting but inconclusive.

This was an Amazon deal that I bought for a buck or two. These are always crapshoots. I have realized two things from these books: editors serve a vital function, and Amazon reviews are unreliable.

I did make it all the way through this one though (even though I skipped long passages).

[Rosann · Rating 4 out of 5]

Definitely not a science book (really not a science book... would have benefitted from a science editor in fact) but a book about living with a rare genetic disease from the person with that disease...

[Roberta · Rating 4 out of 5]

When I went to university I toyed with the idea of studying medicine. Unfortunately I get dizzy in front of blood, so I decided it wasn't my call. That doesn't prevent me from reading about medicine though, which is one of my guilty pleasures.

Here we meet with a family with a peculiar mutation: they die young(ish) due to a faulty gene that no one else has, and it takes decades for their doctors to understand their struggle.

I empathize with the writer: how would I react if I had an unavoidable expiration date? On the same page I also read The Family that Couldn't Sleep, which I highly recommend.

[Jessica - How Jessica Reads · Rating 4 out of 5]

FASCINATING. I couldn't put this down. An intriguingly sad mix of science, genetics, and family tragedies.

[Margie · Rating 4 out of 5]

A teenager watches her father, a doctor, die from a very mysterious disease. His daughter over time starts to find others in her family that died from the same thing. She herself started to show similar problems. This is her story and her search for answers.

[Kate · Rating 3 out of 5]

Sort of interesting genetic mutation in one family. But would have made a better article. Repetitive and side tangents. Author clearly doesn't understand much biochemistry.

[Jessica · Rating 5 out of 5]

Joselin Linder's “The Family Gene” is the incredibly moving story of one woman's quest to understand the deadly genetic disease that has plagued her family for several generations. But, in spite of its tragic subject-matter, this book is ultimately about hope. As a writer, reporter, and self-professed science-nerd, Linder shares both personal and family stories generously, while simultaneously chronicling the decades long search of medical professionals struggling to understand and treat her family's mysterious gene. She follows the manifestations of the disease's strange and varied symptoms as far back as her great-grandmother Mae, sharing her family's oral history, medical records, even entries from the journal of her father, a doctor himself, who struggled tirelessly to understand this mysterious condition that was taking his own life. This book is a complete page turner, and made me laugh as well as cry. It is a fascinating journey. Don't miss it!

[Julie · Rating 5 out of 5]

Joselin Linder writes a book that is one half memoir and another medical mystery. She describes watching her physician father become more and more unwell, while doctors struggle to figure out what is wrong with him. It is not until other family members succumb to the same symptoms and problems, that the family and doctors begin to realize that this disease that only affects their family has a genetic cause.

With advances in genetic testing many of the family bring themselves forward to be tested, and after Joselin and her sister both test positive, it them forces them into making many ethical choices about whether to have children or not and what treatments to undergo, when there is no proven treatment plan.

Fascinating stuff - it makes you wonder what you would do in a similar circumstance and you have to admire her bravery for writing this book.

[Patricia Farley · Rating 5 out of 5]

This was the first book I've won in a Goodreads contest and it was fantastic! I finished it very quickly as it was hard to put down. The book starts off with her dad dying from a mysterious illness which is from a gene passed down through an X chromosome. There are many scientific and medical terms used throughout this book but these terms are explained so they are easily understood. Ms Linder is also found to have this gene and is very honest about what is happening to her and the members of her family. The author tells the story of the research done to find a diagnosis and coming to terms with a possible unhealthy future. Throughout all of this she is positive and optimistic. I recommend this to anyone who is looking for a great book; it's a memoir and nonfiction and a bit of reference all rolled into one.

[Peyton Tracy · Rating 4 out of 5]

This is a fascinating and refreshingly honest memoir that gripped me from beginning to end. It also functions as an informal and conversational introduction to genetics and genetic diseases, their study, and developing treatment. The author stops to explain things as she learns them or as their context becomes important and doesn’t shy away from sharing her opinion on them. She doesn’t shy away from much of anything, honestly, sharing every painful detail of her family’s medical history and tackling a lot of difficult ethical conundrums she and her family and all those with genetic diseases grapple with. I listened to the audiobook and loved every second!

[Bethany Zakrzewski · Rating 3 out of 5]

This is a lovely tribute to a family that underwent a great deal of impossibles. I had to take time reading it because it is full of slow painful deaths. The deviation between this and books like Tuesdays with Morrie is that this shows how health is at the hands of the individual. Not all diseases could be solved like a mystery for sure, and this case took modern scientific advances and very dedicated doctors and researchers. But more importantly, it took a very well-informed and motivated family who collaborated.

[Miriam Kahn · Rating 4 out of 5]

This is the tale of searching for a cure for a rare or "orphan" disease. Lindner's family is dying from mysterious causes. She traces her family tree and finds several other deaths like her father's.

Part investigation, part medicine, Linder teaches readers about genetic testing and gene therapy. You could compare this with The Immortal Life of Henrietta Lacks" with much more science thrown in.

The book is sad and uplifting t the same time. Be forewarned, reading this at night may keep you up until the wee hours.

[Esther Bradley-detally · Rating 5 out of 5]

My last two review disappeared into the ether; this is an excellent book; fraught with horror, courage, tension, maturity, bravery, and deals with current issues. Genetic diseases are cropping up with extreme rapidity, and many are not known about; highly recommend book

[Lauren · Rating 4 out of 5]

More informative than personal, this is the story of a gene that wreaks absolute havoc on multiple generations of a family. I learned so much listening to this audiobook. The writing was great and always to the point. If the topic interests you, you’ll no doubt enjoy this.

[Kirsten Love dipatri · Rating 5 out of 5]

Top notch medical mystery memoir. The writing is excellent, story compelling. So surprised it hasn’t been made into a movie yet. Highly recommend!

[Kirsten Kinnell · Rating 4 out of 5]

Incredibly compelling as both a medical mystery and a memoir. Lovely writing that makes complicated science accessible, and a voice that by turns is hilarious and heart breaking.

[Cassie · Rating 5 out of 5]

Couldn't put it down and read it in one sitting

This book is fascinating and well written. The author does an amazing job of telling a personal story while mixing in the more technical aspects of genes and medicine. I highly recommend this for anyone who likes mysteries, memoirs, and books about diseases.

[Karen · Rating 4 out of 5]

What an interesting book. Well written, easy to read.

[Janis Mills · Rating 4 out of 5]

It takes a certain amount of courage to know how you are going to die according to my belief. The author wrote of her gene pool and the effort and heartache to track down the disease taking family members too young. It was a fascinating story told with courage.

[Cynthia · Rating 5 out of 5]

Very interesting and well written! I love medical-mystery nonfiction!

[Jo · Rating 4 out of 5]

Well written and interesting, but the medical stuff was a little gross and deeply detailed for my taste though I guess I should have expected that going into it. It was a fascinating story of how they are trying to determine the genetic issues that are causing the illnesses in her family.

[Serena · Rating 3 out of 5]

In The Family Gene author Joselin Linder, holder of said gene, writes about the experience of discovering her family was passing a variant and ultimately fatal gene through their family tree. After realizing there might be a problem, her family connects with several doctors who become champions for the family and develop years of time researching their new, unnamed condition.

The book provides plenty of background information on genetics for the uninitiated, and some interest factoids for those familiar with the basics. I definitely wouldn't call this novel "riveting" or a "medical mystery" as advertised, but the writing was solid and the story is interesting. Some of the best parts in my opinion were Linder's reflections on what carrying the variant gene means to her and how she lives with the knowledge of what is wrapped up in her chromosomes. That's something you can't learn from a genetic textbook!

I would recommend this book to fans of medically-oriented non-fiction, though my first pick in that genre will always be the utterly brilliant The Immortal Life of Henrietta Lacks which Linder actually references in her own work.