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Posts from the ‘Syndrome’ Category

Gene Genie: a Famous Blog Carnival’s Sixth Issue

467px-dna_repair.jpgYou may realized that our favourite blog carnival, Gene Genie has been mentioned in the last issue of Cell. So as it became a famous blog carnival with the goal of covering the whole genome before 2082, in the sixth issue, I’m going to mention at least a dozen of posts, articles focusing on genes and gene-related diseases. If you happen to remember the time when I hosted Grand rounds, the weekly blog carnival of the best of the medical blogosphere, you’ll not be astonished by these weird videos of genetics. So let’s get ready to the genes…

My Biotech Life presents a gene called Tbx1 whose inactivation leads to DiGeorge syndrome, a rare congenital disease. He also describes Tbx2/3 transcription factors and their role in embryonic development.

The SciencetificBlogging Team has an article on the genetic aspects of autism. Researchers (University of Iowa) have showed that if a mutation occurs in sperm cells of a father (who doesn’t have autism), it can be passed on to his children.

DNA Direct Talk raised some concerns about the gene discovery for heart disease risk, and made an informative list of facts about Mucolipidosis type IV, a neurodegenerative disorder.

Ok, there are thousands of genes, but what we know about non-coding DNA? Larry Moran at Sandwalk tells us everything of the subject and if you’re there, it’s worth taking a look at the comments. Larry also wrote a well-referenced post on human genes for the pyruvate dehydrogenase complex.

The Afarensis Blog examines this question regarding the Intelligent Design – evolution debate as “when some bit of DNA, thought to be non-coding, looks like it has a function, ID proponents are quick to trumpet this as evidence against evolution”.

If you want to know more about sex chromosomes from an evolutionary point of view, don’t miss Evolgen’s interesting article. Let’s take a break now with a Mendel-rap:

We should continue with clinical genetics and a little bit of fun. Hsien-Hsien Lei has made an interview with Dr. Keith Batchelder, the leader of Genomic Healthcare Strategies, a company focusing on personalized medicine and the intersection of personal genetic information with healthcare.

An amazing case is described by Chris Depelteau at Cool MRI Stuff about the resolution of Chiari malformation after repair. The body is so awesome, isn’t it?

I’m amazed when scientists, physicians present an important issue to the public in a readable and totally understandable style. The genetic genealogist did exactly that by answering some so called “frequently asked questions” about GINA, the Genetic Information Non-Discrimination Act that has recently passed the House of Representatives.

MC at Neurophilosophy introduces a program called Gene2Music which can transcribe any DNA sequence into music. We should make a podcast of the musics generated by all the genes’ sequences mentioned in Gene Genie…

Sorry for including my submission, but this has become a tradition in Gene Genie, so I’d like to share my thoughts with you on PTC124, a new drug against genetic diseases.

And at last, here is the editor’s choice from Control Your Genetic Destiny! The words of Wade Meredith (Kudos!) should be the message of this issue:

Finding out how your helix is stacked is like getting an advanced copy of the test (your health) before the big exam (the rest of your life). If you already know your weaknesses you can fight them head on, instead of trying to play catch-up once your condition is rapidly deteriorating.

I have to say farewell with an other funny video on the magic of genetics with Gregor Mendel. Thank you for watching!

Here are all the issues of Gene genie:

If you’re thinking about hosting an edition, don’t hesitate to contact me at berci.mesko [at]

Update: for more info, please visit!

PTC124, a Drug Against Genetic Diseases: Overview

I’ve already written about the Times Online article (Daily pill to beat genetic diseases), but I would like to give a clear overview of this “miracle-drug”. The story of PTC124 is not new, it goes back to 2004. Anyway, what is it about?

PTC124 is a novel, orally administered small-molecule compound that targets a particular genetic alteration known as a nonsense mutation. Genetic disorders occur as a consequence of mutations in an individual’s DNA. Nonsense mutations are alterations in the DNA that, when transcribed into mRNA, introduce a premature translation termination codon. This change halts the ribosomal translation process at an earlier site than normal, producing a truncated, non-functional protein.


So PTC124 binds to the ribosome, ignores the nonsense mutation, but doesn’t repair it and make the genetic disease “go away” as it makes it possible for the body to produce the proper protein. Just some examples for genetic diseases caused by nonsense mutation (of the approximately 1800 similar diseases):

As it doesn’t repair the mutation, patients have to take the pill throughout their lives. Here is an image, how it works exactly:


OK, it sounds fantastic, but what about the studies?

You can read more about the phase 2 clinical trials of Duchenne muscular dystrophy and cystic fibrosis as well. The description of phase 2 clinical trials for Duchenne muscular dystrophy says:

The results from this study indicate that PTC124 is well-tolerated and imply pharmacological activity based on preliminary data that suggest increases in dystrophin in muscle biopsies in a number of patients and statistically significant improvements in creatine kinase in blood… several parents and teachers have reported that boys participating in the study have had improvements in terms of greater activity and increased endurance during treatment.

Phase 2 clinical trials for Cystic Fibrosis:

Across the two studies, at both PTC124 dose levels tested, TEPD assessments showed statistically significant improvements of average CFTR-dependent chloride secretion in the airwaysAlthough a formal symptom assessment was not a component of the Phase 2 program, a number of patients described decreased sputum volume and thickness, decreased frequency and severity of coughing and a better sense of well-being during PTC124 therapy.

I have to admit that these results are incredible, look how dystrophin was rebuilt:


It also sounds great, though I think we should be a little skeptic as new therapies are always presented as miracle methods in spite of side effects and non-expected mistakes. Anyway, it might be a really exceptional improvement in the future. I’m eagerly waiting for the results of the next clinical trials. Until then, in case you’re still interested, read more about PTC124:

Related links:

Superhuman power, 2 hearts and Youtube in medicine

Sorry for not posting long, serious articles (by the way, the blogterview about robotics and medicine is almost ready), but I’ve been really busy at the university, so this time again I show you some of my favourite links for today:

Photographic memory, Tertiary Neurosyphilis, Synesthesia, Savantism without major autistic impairments, Temporal Lobe Epilepsy, Congenital Insensitivity to Pain, Persistent Sexual Arousal Syndrome and Hypergraphia. Don’t miss it!

Fascinating images and EKG from the NEJM of a patient who had a heart transplant, but the native heart was left in.

It’s exciting to see more scientists start using web2.0 products such as youtube, google video, social bookmarking sites like furl, stumbleupon , netvouz, del-ic-ious and blogs and wikipedia. The BioIt magazine has published the following article on the trend.

And the most important finding:

Research studies demonstrating the viability of an approach to routinely detect the presence of fetal DNA in a mother’s blood to accurately diagnose or rule out genetic defects — as early as the first trimester — was presented at the 27th Annual Meeting of the Society for Maternal-Fetal Medicine held in San Francisco. This future diagnostic technology, currently under development at Sequenom, Inc. shows promise that a universal alternative to such invasive genetic screening procedures as amniocentesis and chorionic villus sampling, may be available in the future.


Pompe disease, a rare but important genetic condition

As I plan to become a clinical geneticist, I should write more often about genetic conditions. But I don’t want to duplicate the articles of Wikipedia, my aim is to provide useful sources of information. Pompe disease is a rare disorder caused by the deficiency of the acid alpha-glucosidase enzyme. It’s inherited in an autosomal recessive manner. The patients can’t break down glycogen. According to the Wiki article:

It is the only glycogen storage disease with a defect in lysosomal metabolism, and was the first glycogen storage disease to be identified—in 1932. The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.

I’d like to show you the main characteristics of the disease and of the diagnosis.

Head lag caused by muscle weakness

Cardiomegaly in Infant


The heart of a 9 month old child who died of congestive failure. (Original material by Horton Johnson)

Why do we have to talk about Pompe? The reason is diagnostic delay. The diagnosis often poses a dilemma due to the rarity of the disease, the variable rates of progression and the unspecific phenotypic features. What kind of disorders do we have to list as a part of the differential diagnosis?

  • Spinal muscular atrophy
  • Hypothyroidism
  • Endocardial fibroelastosis
  • Myocarditis
  • Congenital muscular dystrophy
  • Glycogen storage diseases
  • Mitochondrial, peroxisomal diseases
  • Danon disease
  • Myasthenia gravis, Becker’s muscular dystrophy

Just take a look at the diagnostic delay diagram, there are from 2 to 4 years between the first symptoms and the diagnosis:


How can we confirm diagnosis? An acid-glucosidase (GAA) assay can be performed on skin fibroblasts or muscle biopsy. A non-invasive and relatively reliable test is GAA assay in blood collected on filter paper. But laboratory testing and molecular analysis must be also taken into consideration.

Some words about the treatment. Of course, genetic counseling can help parents as it provides them information about a possible future pregnancy. According to the wiki article:

On April 28, 2006 the US Food and Drug Administration approved a biologics license application (BLA) for Myozyme (alglucosidase alfa, rhGAA), the first treatment for patients with Pompe disease primarily developed by Dr. Yuan-Tsong Chen while he was at Duke University. Myozyme falls under the FDA Orphan Drug designation and was approved under a priority review.

Although Pompe disease is a rare condition (estimated to occur in about 1 in 40,000-300,000 births), it should get much more attention as the diagnostic delay still means a crucial problem in treating these children.


Bye Bye, Sonic Hedgehog

sonichedgehog.jpgI planned to make a good start for Gene Genie but my first gene related post is about a farewell. Sonic Hedgehog, one of the most famous genes, will lost his name. According to the Discover article:

An international committee of human geneticists recently voted to change the names of a few human genes because the current, sometimes flamboyant names—like Sonic hedgehog—are either offensive or embarrassing… The vote was conducted by the HUGO Gene Nomenclature Committee, which establishes naming protocols for human genes.

The gene map locus is 7q 36 . Sonic Hedgehog regulates vertebrate organogenesis, the growth of digits on limbs and organisation of the nervous system (brain, spinal cord, thalamus, zona limitans interthalamica). Additionally, fruit flies with a mutation in this gene don’t have external genitalia.

The so called hedgehog gene (hh) was first identified in 1978 as a morphogen. Sonic got his weird name after a phenomenon well described in the Wikipedia article: the hh loss of function mutant phenotype causes the embryos to be covered with denticles (small pointy projections), much like a hedgehog.

What kind of disorders is this gene responsible for?

  • Holoprosencephaly type 3: cerebral disorder characterized by the failure of the prosencephalon (forebrain) development in the embryo.
  • Ocular Colobomas: eye related malformations that result from a defect in the fusion of the fetal optic fissure
  • Preaxial Polydactyly II: anatomical variant consisting of more than the usual number of digits on the hands and/or feet.
  • Cleft Lip and/or Palate

Click to enlarge!

Zebrafish embryo with a stain that shows where the hedgehog protein is acting during development.

References :

Update! One additional sentence from the Wikipedia article: many “[call] it inappropriate that patients with ‘a serious illness or disability are told that they or their child have a mutation in a gene such as Sonic hedgehog.’” (Thank you, Darmok, for the suggestion!)

A New Year’s baby’s newborn screening

So good to read something like that. I’m always talking about newborn screening and prevention. I hope to see many more improvements just like this one:

Jaylen Jeremiah Jenkins is a New Year’s baby, and one the first in the state of Georgia to be screened for 28 disorders instead of only 12… And although born a few weeks early, he seems to be a happy and healthy boy. The cost for these new tests is now $40 and is covered by insurance.

The Georgia Newborn Screening Program is now over two decades old. From January 1, 2007, every live born infant must have an adequate blood test for 28 disorders (the most common disorders in the first line, the rarer ones in the other lines):

  • Phenylketonuria, Congenital Hypothyroidism, Maple Syrup Urine Disease, Galactosemia, Tyrosinemia, Homocystinuria, Congenital Adrenal Hyperplasia, Biotinidase Deficiency, Sickle Cell Disorders (SS, SC, S-beta thalassemia), Cystic Fibrosis
  • Medium-Chain Acyl-CoA Dehydrogenase Deficiency, Isovaleric acidemia, Glutaric acidemia type I, 3-OH 3-CH3 glutaric aciduria (HMG), Multiple carboxylase deficiency, Methylmalonic acidemia, 3-Methylcrotonyl-CoA carboxylase deficiency (3MCC), Propionic acidemia, Beta-ketothiolase deficiency, Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD), Long-chain L-3-OH acyl CoA dehydrogenase deficiency (LCHAD), Trifunctional protein deficiency, Carnitine uptake defect, Citrullinemia, Argininosuccinic acidemia.

Now, we can see how to improve our system. A really great effort from the state of Georgia.



Interview with Shane McKee, a clinical geneticist (part one)

Dr Shane McKee MD BSc MRCPCH FRCP(Edin) is a consultant clinical geneticist at the Northern Ireland Regional Genetics Service in Belfast. I’ve found him as the webmaster of several genetics related sites such as the Irish Society of Human Genetics or the Clinical Genetics Society. He has been given the ISHG Young Investigator Award for the best oral presentation at the ISHG annual conference about Benign Familial Infantile Convulsions – a clinically and genetically heterogeneous disorder. He was very kind when I asked him to answer some of my questions. Here is the first part of the interview:

  • How and why have you become a clinical geneticist?

Even from before I became a doctor, I was interested in Clinical Genetics, and the role of genetics in the development of humans and other species. Genetic factors underpin a huge amount of the variation in the population, including our susceptibility to disease. At medical school (Queen’s University Belfast) I took a year out of my medical studies to get an intercalated degree in Medical Genetics. I could see that genetics was a field of medicine that promised to revolutionise our understanding of human biology and disease. I still believe that this is the case. But what makes any aspect of medicine worthwhile is the interaction with patients and families. Educating patients in the causes and management of their own conditions can be incredibly rewarding.

  • Which fields are you specialized in?

I practice quite a wide range of genetics, and see a very wide range of conditions, from prenatal to general to dysmorphology through to cancer genetics. In some ways, Genetics is one of the last truly general hospital specialties – we can see anything and everything! This is not surprising, because the majority of human disease has at least some genetic element. However, many of us are becoming increasingly specialised, as a result of the sheer breadth of conditions that we have to see. One area of particular interest to me is epilepsy genetics. This is becoming increasingly important as more of the genes causing epilepsy are found, and we’re starting to see how different anti-epileptic drugs might work.


  • What are the most often genetic conditions, disorders in your region?

In Northern Ireland we see pretty much the same range of conditions as elsewhere in Europe, although the rates of cystic fibrosis and haemochromatosis are a bit higher here. We also have some population subgroups, such as the Irish Travellers, who have a high rate of disorders such as mucopolyaccharidosis type 1H (Hurler syndrome) and I-cell disease. We also see a lot of hereditary bowel and breast cancer, which is also the case in the rest of Europe.



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