Overview of Trinucleotide Repeat Disorders

Welcome back guys. Now, let's continue with the trinucleotide repeat disorders. Already in the previous video, we have discussed about the mitochondrial inheritance which does not follow the Mendel's laws of inheritance, non-Mendelian disorders. Now, let's begin with the trinucleotide repeat disorders. Trinucleotide repeat disorders which means A trinucleotide sequence is going to repeat many number of times. Okay, in a gene, say for example there is a trinucleotide, call as a CAG. Now it's going to repeat 10 times, 20, 30, 40, 50, 100, 200 times. That same repeat, trinucleotide repeat is going to repeat many number of times. So, which is going to cause trinucleotide repeat disorders. Okay. Now, what are the examples of trinucleotide repeat disorders? There are four important such examples which you need to know for your exam. The first example is Huntington's disease. Huntington's disease. Second, Fragile X syndrome. Fragile X syndrome. Friedrich Ataxia, Myotonic Dystrophy. Okay, Myotonic Dystrophy. So, all these are examples of trinucleotide repeat disorders. See, the Huntington's disease, you can ask me, so what are the trinucleotides that are getting repeated in all these conditions? So, in all these conditions, there is one trinucleotide which is getting repeated, right? See, in Huntington's disease, the trinucleotide repeat is a CAG repeats okay CAG 16 adenogonin it's the same time you could it it's going to repeat many number of times in Frederick's a infragile X syndrome it is a CGG in Frederick ataxia okay ataxia means a gate problem right ataxia means a gate abnormality right so I used to remember like GA okay gate GA IT gate something like that okay so gate abnormality myotonic dystrophy so myotonic tonic So, CTG, okay, tonic. So, CTG, okay, CAG, CGG, GAA, it's GAA for the gait abnormality, that's the Friedrich's ataxia and CTG for myotonic dystrophy, okay. So, these are the trinucleotide repeat diseases and these are the trinucleotides which are getting repeated. Now, having said that, now in this video. First, let's begin with the condition that is called as the Fragile X Syndrome. First, in this video, we will discuss about the Fragile X Syndrome as well as the Myotonic Dystrophy. In the next video, we will be discussing about the Huntington's Disease as well as the Friedrich's Ataxia. We will be discussing in the next subsequent videos. So, first, let's begin with the Fragile X Syndrome. So, in Fragile X Syndrome, what I want you to know is, so in Fragile X Syndrome, what is the main problem? So, Fragile X Syndrome follows X-linked recessive inheritance pattern. It follows X-linked recessive inheritance pattern. See, in last videos, we have discussed that in X-linked recessive disorders, which sex is going to be mainly affected? Males are mainly affected. Mainly affected. with this fragile X syndrome. Now see this is the normal X right, this is the normal X, X and Y chromosomes are there, this is the normal X. Now in fragile X syndrome if you look at the X, see that if you do the staining of the X, see this portions of the X chromosome are not going to take the stain that portions are not going to get stained so how it is looking like so the chromosome is looking like it's having a fragile end fragile tip so that tip at any point of time it might be separated it looks like that it gives an appearance like that but it's simple that that part of chromosome is not getting strain. So, that's why it's called as a fragile X syndrome. Okay, fragile X syndrome. So, this fragile X syndrome, it follows which inheritance pattern, X-linked ratio inheritance pattern, mainly males are going to be affected. Now, what is the gene mutation? The gene mutation which is seen here, the gene mutation is going to be FMR gene mutation, FMR1. What exactly is FMR1, sir? If you ask me, familial mental retardation. Okay, the gene is familial FMR1. mental retardation gene. So, familial mental retardation, one gene mutation. So, because of this gene mutation, FMR1 gene mutation, so the CAG repeats are going to be multiplied. See, the point which I want you to know is in you and me, do we have CAG repeats? Yes, absolutely, we have the CAG repeats. Okay, but less than 55, less than 55 CAG repeats are considered as normal. Less than 55 repeats are normal. See, from 55 to 200, if a person is having 55 to 200 repeats, it is considered as a pre-mutation. It's considered as pre-mutation. Pre-mutation fragile X tremors. These patients are going to have pre-mutation fragile X tremors. If a person is having more than 200 repeats, then it is fragile X syndrome. This is the proper Fagellek syndrome. So, usually in you and me, we have the CAG repeats, okay, CAG repeats. Sorry, the point which I want to change here is not CAG repeats. Sorry, CAG repeats are going to be seen in Huntington's, okay. So, here it is CGG, sorry, CGG repeats. So, CGG repeats are going to be there. Less than 55 repeats, that's okay. Okay, less than 55 repeats, that's okay. If the repeats are more than, okay, 55 to 200, in between 55 to 200, it's called a pre-mutation. Less than, Sorry, more than 200 is called the fragile X syndrome. Okay. Now, let's see what the clinical features. If a patient is having fragile X syndrome, what are the clinical features? Let me show you how the patient is going to look like. See, if a patient is having the fragile X syndrome, here I forgot to paste the image, he is going to have a very long face. Okay. He is going to have a very long face. Okay. Long face, long ears. okay long mandible see i highly request you to just watch this in the youtube or in google so how the face is going to look like he's going to have a long face okay elongated face elongated ears large mandible is going to be seen so all these things are going to be seen but the one point which i want you to know is the nose is normal nose is normal you ok everything is lost everything is long but no see like normal even especially seen in males right males and stashes ok so testes is also going to be big ok so large testes ok so post pubertal means after puberty so after puberty the testes size is going to be very much large so large this is a scholar macro architism ok macro architism large testes are macroarchidism. So in this cardiovascular system these patients with the Frederick syndrome are going to have mitral valve prolapse. Mitral valve prolapse that's going to give you the murmurs. okay my tell all collapse causes the murmurs now females yes females can also get the disease but that's a very rare but most of the time females are going to be carriers okay excellent to receive these orders females are going to be carriers females are carriers so for example if the female is having this like you know carrier state now she is going to have premature ovarian failure Usually ovarian failure happens by 45 years or 50 years. That's a menopause. But before 30 years, she's going to get the ovarian failure. Okay. So that's the point which I want you to know. So this condition, it follows a paradox called a Sherman's paradox. Sherman's paradox. This trinucleotide repeat disorders not only just this thing one thing but other trinucleotide disorders they follow the paradox called as the Sherman paradox. So what exactly is this Sherman paradox? Sherman paradox means anticipation. Okay anticipation. So, what exactly is this anticipation, sir? If you ask me, anticipation means, for example, there is this father. Okay, father, he is having a disease. That is Fragile X Syndrome. Father is having a disease, Fragile X Syndrome. He manifested the disease, for example, by 30 years of age or 40 years of age. Okay, he manifested the disease by 40 years of age. Okay, now he is having, for example, 200 repeats. 200 repeats are there in the father. Or 200 repeats or 210 repeats are there, for example. ok now in the next generation the number of repeats are going to be increased the number of repeats will be increased in the next subsequent generation the number of repeats are going to be increased so with every generation the number of repeats increases the more number of repeats the more early the diseases going to get manifest. So you can anticipate, okay, if father is having a disease by 40 years, you will be getting by 35 years. More number of repeats, more early the disease is going to get manifest. Okay, in the next generation, more number of repeats, more early the disease is going to get manifest. So what you can do is, you can anticipate that, like how early you can get the disease based on the number of repeats. So let me write here, with every generation, The body Sherman's paradox with every generation repeats increases, repeats increases and severity of the disease also, severity of disease also increases. Okay, so this is the point which I want you to know regarding the fragile X syndrome. So, one of the important points which you should know regarding the fragile X syndrome is that X chromosome is going to not stain properly. So, it's going to look like a fragile X. What is the repeat? The repeat is going to be CGG repeat. Because of gene mutation, FMR1 gene mutation. FMR1 stands for familial mental retardation. The face is going to be long. The ears are going to be long. The mandible is going to be long. But the nose is going to be of normal size. Post pubertal, these fellows are going to have a bigger test. That is called as a macroarchidism. In females who are the carriers, most of the time they will be having premature ovarian failure. And what is the Sherman's paradox? With every generation, the number of repeats increases as well as the severity of the disease also increases. And one more thing, what you can do is the anticipation. If a father is having a disease by 50 years, the son is going to get the disease by 45 years or 40 years. With every generation, the early the disease is going to get manifest. So, after this, the next trinucleotide repeat disorder, see, one thing is completed. Fragile syndrome, we have completed. The next trinucleotide repeat disorder that I want you to know is myotonic dystrophy. Okay, myotonic tonic CTG. Okay, so, let's discuss about the myotonic dystrophy. Okay, myotonic dystrophy. See, in myotonic dystrophy, what is the repeats? Only the important points I am writing here. What is the repeats? CTG repeats. ok ctg repeats next it is following which inheritance pattern familial sorry fragile x syndrome is following the x negative inheritance pattern is going to follow autosomal dominant ok already in the the list i have given You can see over there, myotonic dystrophy. Myotonic dystrophy follows autosomal dopamine inheritance pattern. See, what these patients, the keywords they will use. See, for example, if you ask me to have a grip on this pen. Okay, this pencil, lapin pencil. If you ask me to have a grip, yeah, I'm having the grip, right? Now, if you ask me to release, I can immediately release the grip. Okay, I can immediately release the grip. But these patients, after having a grip, it's hard for them to release the grip. Okay, it's hard for them to release the grip. So, that's a keyword. So, difficulty. ok in releasing the grip. So difficulty in releasing the grip. Now if you look into their eyes, see here it is given if you look into their eyes it's going to look like a lighten up Christmas tree. Ok so what you will see is that cataracts, Christmas tree cataracts. Ok Christmas tree cataract. Christmas tree cataracts are going to be seen and if you look at their faces okay if you look at their faces see they're going to have the frontal balding is going to be seen and they you classically use this word which is called as a hatchet faces okay hatchet faces okay so the face is going to see their face is going to look like a hatchet hatchet faces are going to be seen Hatchet faces balding is going to be seen and see see there is balding right so male pattern baldness Okay, male pattern baldness Next what else you should know is sir in the previous condition of the fragile X syndrome Okay, everything is long long face long bandible long ears testics big big big test is see this patient with a myotonic dystrophy They are going to have the testicular atrophy testicular atrophy and if you look into their heart, the heart is going to be big that is cardiomyopathies can be seen, sorry not big so cardiomyopathies are going to be seen which can lead to the heart blocks cardiomyopathies which can lead to heart blocks that can actually cause the arrhythmias These patients are at risk of having arrhythmias. Male pattern baldness, arrhythmias, cardiomyopathy is going to be seen. So, see myotonic. These patients are going to have muscular atrophy. Muscular atrophy. One more thing. As well as, these patients are going to have respiratory difficulties. okay muscle related problems muscular related problems so respiratory difficulty even because the diaphragm is a muscle so at the end of the day the points which i want you to know is here i have discussed two trinucleotide repeat disorders one is fragile x syndrome the other is myotonic dystrophy in myotonic dystrophy simple artosomal dominant hindrance pattern facet facet facet faces baldness is going to be seen male pattern baldness testicular atrophy is going to be seen muscular weakness is going to be seen heart related problems heart is a muscle so cardiomyopathies which can lead to arrhythmias due to the heart blocks desperate difficulties are going to be seen if you look into the eyes Christmas tree cataracts the most important out of all is Christmas tree cataracts autosomal dominant CTG repeats okay and testicular atrophy these are the important points hazard faces so these are the keywords which will be used okay for myotonic dystrophy you can very clearly see here see difficulty in releasing the grip okay if you ask this person to release the grip It is very difficult for him to release the grip. Okay. So, with this, we have completed the two trinucleotide repeat disorders. In the next video, we will be discussing about the Huntington's. Okay. Huntington's chorea as well as Friedrich's ataxia in the next video. Hope the video is helpful. Thank you.

Trinucleotide repeat disorders which means A trinucleotide sequence is going to repeat many number of times. Okay, in a gene, say for example there is a trinucleotide, call as a CAG. Now it's going to repeat 10 times, 20, 30, 40, 50, 100, 200 times. That same repeat, trinucleotide repeat is going to repeat many number of times. So, which is going to cause trinucleotide repeat disorders.

Okay. Now, what are the examples of trinucleotide repeat disorders? There are four important such examples which you need to know for your exam.

The first example is Huntington's disease. Huntington's disease. Second, Fragile X syndrome.

Fragile X syndrome. Friedrich Ataxia, Myotonic Dystrophy. Okay, Myotonic Dystrophy.

So, all these are examples of trinucleotide repeat disorders. See, the Huntington's disease, you can ask me, so what are the trinucleotides that are getting repeated in all these conditions? So, in all these conditions, there is one trinucleotide which is getting repeated, right? See, in Huntington's disease, the trinucleotide repeat is a CAG repeats okay CAG 16 adenogonin it's the same time you could it it's going to repeat many number of times in Frederick's a infragile X syndrome it is a CGG in Frederick ataxia okay ataxia means a gate problem right ataxia means a gate abnormality right so I used to remember like GA okay gate GA IT gate something like that okay so gate abnormality myotonic dystrophy so myotonic tonic So, CTG, okay, tonic.

So, CTG, okay, CAG, CGG, GAA, it's GAA for the gait abnormality, that's the Friedrich's ataxia and CTG for myotonic dystrophy, okay. So, these are the trinucleotide repeat diseases and these are the trinucleotides which are getting repeated. Now, having said that, now in this video.

First, let's begin with the condition that is called as the Fragile X Syndrome. First, in this video, we will discuss about the Fragile X Syndrome as well as the Myotonic Dystrophy. In the next video, we will be discussing about the Huntington's Disease as well as the Friedrich's Ataxia.

We will be discussing in the next subsequent videos. So, first, let's begin with the Fragile X Syndrome. So, in Fragile X Syndrome, what I want you to know is, so in Fragile X Syndrome, what is the main problem? So, Fragile X Syndrome follows X-linked recessive inheritance pattern. It follows X-linked recessive inheritance pattern.

See, in last videos, we have discussed that in X-linked recessive disorders, which sex is going to be mainly affected? Males are mainly affected. Mainly affected.

with this fragile X syndrome. Now see this is the normal X right, this is the normal X, X and Y chromosomes are there, this is the normal X. Now in fragile X syndrome if you look at the X, see that if you do the staining of the X, see this portions of the X chromosome are not going to take the stain that portions are not going to get stained so how it is looking like so the chromosome is looking like it's having a fragile end fragile tip so that tip at any point of time it might be separated it looks like that it gives an appearance like that but it's simple that that part of chromosome is not getting strain.

So, that's why it's called as a fragile X syndrome. Okay, fragile X syndrome. So, this fragile X syndrome, it follows which inheritance pattern, X-linked ratio inheritance pattern, mainly males are going to be affected. Now, what is the gene mutation? The gene mutation which is seen here, the gene mutation is going to be FMR gene mutation, FMR1.

What exactly is FMR1, sir? If you ask me, familial mental retardation. Okay, the gene is familial FMR1. mental retardation gene.

So, familial mental retardation, one gene mutation. So, because of this gene mutation, FMR1 gene mutation, so the CAG repeats are going to be multiplied. See, the point which I want you to know is in you and me, do we have CAG repeats?

Yes, absolutely, we have the CAG repeats. Okay, but less than 55, less than 55 CAG repeats are considered as normal. Less than 55 repeats are normal.

See, from 55 to 200, if a person is having 55 to 200 repeats, it is considered as a pre-mutation. It's considered as pre-mutation. Pre-mutation fragile X tremors. These patients are going to have pre-mutation fragile X tremors.

If a person is having more than 200 repeats, then it is fragile X syndrome. This is the proper Fagellek syndrome. So, usually in you and me, we have the CAG repeats, okay, CAG repeats. Sorry, the point which I want to change here is not CAG repeats. Sorry, CAG repeats are going to be seen in Huntington's, okay.

So, here it is CGG, sorry, CGG repeats. So, CGG repeats are going to be there. Less than 55 repeats, that's okay. Okay, less than 55 repeats, that's okay.

If the repeats are more than, okay, 55 to 200, in between 55 to 200, it's called a pre-mutation. Less than, Sorry, more than 200 is called the fragile X syndrome. Okay. Now, let's see what the clinical features.

If a patient is having fragile X syndrome, what are the clinical features? Let me show you how the patient is going to look like. See, if a patient is having the fragile X syndrome, here I forgot to paste the image, he is going to have a very long face. Okay. He is going to have a very long face.

Okay. Long face, long ears. okay long mandible see i highly request you to just watch this in the youtube or in google so how the face is going to look like he's going to have a long face okay elongated face elongated ears large mandible is going to be seen so all these things are going to be seen but the one point which i want you to know is the nose is normal nose is normal you ok everything is lost everything is long but no see like normal even especially seen in males right males and stashes ok so testes is also going to be big ok so large testes ok so post pubertal means after puberty so after puberty the testes size is going to be very much large so large this is a scholar macro architism ok macro architism large testes are macroarchidism.

So in this cardiovascular system these patients with the Frederick syndrome are going to have mitral valve prolapse. Mitral valve prolapse that's going to give you the murmurs. okay my tell all collapse causes the murmurs now females yes females can also get the disease but that's a very rare but most of the time females are going to be carriers okay excellent to receive these orders females are going to be carriers females are carriers so for example if the female is having this like you know carrier state now she is going to have premature ovarian failure Usually ovarian failure happens by 45 years or 50 years.

That's a menopause. But before 30 years, she's going to get the ovarian failure. Okay. So that's the point which I want you to know. So this condition, it follows a paradox called a Sherman's paradox.

Sherman's paradox. This trinucleotide repeat disorders not only just this thing one thing but other trinucleotide disorders they follow the paradox called as the Sherman paradox. So what exactly is this Sherman paradox?

Sherman paradox means anticipation. Okay anticipation. So, what exactly is this anticipation, sir?

If you ask me, anticipation means, for example, there is this father. Okay, father, he is having a disease. That is Fragile X Syndrome.

Father is having a disease, Fragile X Syndrome. He manifested the disease, for example, by 30 years of age or 40 years of age. Okay, he manifested the disease by 40 years of age. Okay, now he is having, for example, 200 repeats. 200 repeats are there in the father.

Or 200 repeats or 210 repeats are there, for example. ok now in the next generation the number of repeats are going to be increased the number of repeats will be increased in the next subsequent generation the number of repeats are going to be increased so with every generation the number of repeats increases the more number of repeats the more early the diseases going to get manifest. So you can anticipate, okay, if father is having a disease by 40 years, you will be getting by 35 years.

More number of repeats, more early the disease is going to get manifest. Okay, in the next generation, more number of repeats, more early the disease is going to get manifest. So what you can do is, you can anticipate that, like how early you can get the disease based on the number of repeats. So let me write here, with every generation, The body Sherman's paradox with every generation repeats increases, repeats increases and severity of the disease also, severity of disease also increases.

Okay, so this is the point which I want you to know regarding the fragile X syndrome. So, one of the important points which you should know regarding the fragile X syndrome is that X chromosome is going to not stain properly. So, it's going to look like a fragile X.

What is the repeat? The repeat is going to be CGG repeat. Because of gene mutation, FMR1 gene mutation. FMR1 stands for familial mental retardation. The face is going to be long.

The ears are going to be long. The mandible is going to be long. But the nose is going to be of normal size.

Post pubertal, these fellows are going to have a bigger test. That is called as a macroarchidism. In females who are the carriers, most of the time they will be having premature ovarian failure. And what is the Sherman's paradox?

With every generation, the number of repeats increases as well as the severity of the disease also increases. And one more thing, what you can do is the anticipation. If a father is having a disease by 50 years, the son is going to get the disease by 45 years or 40 years. With every generation, the early the disease is going to get manifest. So, after this, the next trinucleotide repeat disorder, see, one thing is completed.

Fragile syndrome, we have completed. The next trinucleotide repeat disorder that I want you to know is myotonic dystrophy. Okay, myotonic tonic CTG.

Okay, so, let's discuss about the myotonic dystrophy. Okay, myotonic dystrophy. See, in myotonic dystrophy, what is the repeats?

Only the important points I am writing here. What is the repeats? CTG repeats.

ok ctg repeats next it is following which inheritance pattern familial sorry fragile x syndrome is following the x negative inheritance pattern is going to follow autosomal dominant ok already in the the list i have given You can see over there, myotonic dystrophy. Myotonic dystrophy follows autosomal dopamine inheritance pattern. See, what these patients, the keywords they will use.

See, for example, if you ask me to have a grip on this pen. Okay, this pencil, lapin pencil. If you ask me to have a grip, yeah, I'm having the grip, right? Now, if you ask me to release, I can immediately release the grip.

Okay, I can immediately release the grip. But these patients, after having a grip, it's hard for them to release the grip. Okay, it's hard for them to release the grip.

So, that's a keyword. So, difficulty. ok in releasing the grip.

So difficulty in releasing the grip. Now if you look into their eyes, see here it is given if you look into their eyes it's going to look like a lighten up Christmas tree. Ok so what you will see is that cataracts, Christmas tree cataracts.

Ok Christmas tree cataract. Christmas tree cataracts are going to be seen and if you look at their faces okay if you look at their faces see they're going to have the frontal balding is going to be seen and they you classically use this word which is called as a hatchet faces okay hatchet faces okay so the face is going to see their face is going to look like a hatchet hatchet faces are going to be seen Hatchet faces balding is going to be seen and see see there is balding right so male pattern baldness Okay, male pattern baldness Next what else you should know is sir in the previous condition of the fragile X syndrome Okay, everything is long long face long bandible long ears testics big big big test is see this patient with a myotonic dystrophy They are going to have the testicular atrophy testicular atrophy and if you look into their heart, the heart is going to be big that is cardiomyopathies can be seen, sorry not big so cardiomyopathies are going to be seen which can lead to the heart blocks cardiomyopathies which can lead to heart blocks that can actually cause the arrhythmias These patients are at risk of having arrhythmias. Male pattern baldness, arrhythmias, cardiomyopathy is going to be seen. So, see myotonic. These patients are going to have muscular atrophy.

Muscular atrophy. One more thing. As well as, these patients are going to have respiratory difficulties.

okay muscle related problems muscular related problems so respiratory difficulty even because the diaphragm is a muscle so at the end of the day the points which i want you to know is here i have discussed two trinucleotide repeat disorders one is fragile x syndrome the other is myotonic dystrophy in myotonic dystrophy simple artosomal dominant hindrance pattern facet facet facet faces baldness is going to be seen male pattern baldness testicular atrophy is going to be seen muscular weakness is going to be seen heart related problems heart is a muscle so cardiomyopathies which can lead to arrhythmias due to the heart blocks desperate difficulties are going to be seen if you look into the eyes Christmas tree cataracts the most important out of all is Christmas tree cataracts autosomal dominant CTG repeats okay and testicular atrophy these are the important points hazard faces so these are the keywords which will be used okay for myotonic dystrophy you can very clearly see here see difficulty in releasing the grip okay if you ask this person to release the grip It is very difficult for him to release the grip. Okay. So, with this, we have completed the two trinucleotide repeat disorders. In the next video, we will be discussing about the Huntington's. Okay.

Huntington's chorea as well as Friedrich's ataxia in the next video. Hope the video is helpful. Thank you.

Transcript for:Overview of Trinucleotide Repeat Disorders

Transcript for:
Overview of Trinucleotide Repeat Disorders