Thursday, November 27, 2014

Prevalence .....

The prevalence of ‘Cutis Laxa’ is estimated 1 in every 1,000,000 birth.


Cutis Laxa is extremely rare. As per National Institute of Health, only around 200 families are suffering from this disorder, worldwide.


Tuesday, November 25, 2014

The Name .....



The term ‘Cutis Laxa’ is a Latin word which means ‘Loose/Lax Skin


Wednesday, November 19, 2014

Cutis Laxa is all about ……

In a one liner Cutis Laxa is a rare inherited connective tissue disorder, characterized by inelastic saggy skin, with droopy appearance.


Connective tissue is the body’s supporting framework of tissue consisting of strands of collagen, elastic fibers between muscles and around muscle groups, blood vessels and simple cells. Connective tissue provides stricture and strength to the muscles, joints, organs and skin.


Tuesday, November 18, 2014

Meet the Little Yuxin ..... (2/2)

The little, Yuxin Xiaoli was born with a loosening skin. Her tiny face is full of wrinkles. The skin on her cheeks and chins drooped. She had even more sagging skin in other parts of her body.

Маленькая девочка выглядит как старушка

Przerażająca choroba! Ta "babcia" ma... 18 miesięcy

The little girl¿s face is covered with wrinkles, and the skin on her cheeks hangs. The skin on her body is even looser


Przerażająca choroba! Ta "babcia" ma... 18 miesięcy

Przerażająca choroba! Ta "babcia" ma... 18 miesięcy

Yuxin’s health is deteriorating ¾ she is suffering from a congenital heart disease, pneumonia and asthma, which recurring frequently these days.



Sunday, November 16, 2014

Meet the Little Yuxin ..... (1/2)

Meet Yuxin Xiaoli, a 3 year old girl in China ¾ but wait a minutes isn’t she looks like 60 ???

What Happened to her ??

Yuxin Xiaoli is thought be suffering from  cutis laxa, which is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds.Yuxin Xiaoli is thought be suffering from  cutis laxa, which is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds

Most of you are thinking that she might be suffering from a premature aging disorder ¾ Progeria??

Nope ----- not at all !!


It’s the rare skin disorder ¾ Cutis Laxa, which makes her look like an old woman.


Monday, November 10, 2014

Meet Zara ..... (2/3)

Zara and her sister Jolene and mum Tracy suffers from a rare disorder ¾ Cutis Laxa, though it was misdiagnosed as ‘Lipodystrophy’ earlier, which causes their skin appears saggy but not stretchy pointing to the premature aging.

lipodystropy family
 Tracey Gibson: 42, and two daughter Jolene Hardy: 24 and Zara Hartshorn: 16

Cutis Laxa is a rare genetic condition in which deterioration in the fatty and connective tissues as well as bones under the skin appears as the extreme premature aging. Some of them reported that their teeth fall out and have had to rely on collagen injection to combat wrinkles.



In contrast to 'Cutis Laxa', ‘Lipodystrophy’ is an extremely rare disorder in which fat deposited in the body parts, where it should not be allowed to deposit. With other health complication 'Lipodystrophy' makes a person look and appear older than his/her original age.



Wednesday, November 5, 2014

Meet Zara ..... (1/3)

Meet Zara Hartshorn, a British lady whose rare genetic condition has made her appear as 60, as if she is in the twilight of her life ¾ her teeth are falling out and she is on collagen injections for her wrinkles ¾  but Zara is no longer a middle aged woman who is coping to rejuvenate her youth ¾ she is only in her 16 !!!

Zara Hartshorn



Zara Hartshorn

Zara with her Birth Certificate

Zara Hartshorn


Thursday, October 30, 2014

Benjamin Button Disorder !!!

When I was a child I often put my feet in my dad’s shoe and start behaving like him ….. I always had a dread of commanding …… I always wished if I could grow up in the very next morning I would also be like my father …… I am sure many of us have this kind of thought at some point of time in childhood ……

But have you guys ever thought what if someone threats you as mom/granny when you are just in your sweet 16 ???

Found any resemblance with the move 'The Curious Case of Benjamin Button' played by Brad Pitt  ¾¾

You are right !!!

My next posts will be discussing on the Reverse Benjamin Button Disorder

Keep Reading J




Tuesday, September 16, 2014

POLH gene cause Xeroderma Pigmentosum (XP)...

POLH gene shows 30+ mutations in the variant type of Xeroderma Pigmentosum (XP-V), which is characterized by increased sensitivity to UV rays from sunlight like the other forms of XP. However, XP-V do not associated with neurological abnormalities such as delayed development and hearing loss.


Most of the mutations in POLH gene prevent the production of any detectable DNA polymerase eta. As we know without DNA polymerase eta cells could not effectively replicate damaged DNA. Without DNA replication for damaged DNA, errors resulting from exposure to UV rays accumulate in the genes which control cell growth and division. Due to this damage, cell growth become uncontrollably fast resulting an increased risk of developing skin cancer in the sunlight exposed areas in the XP-V affected individual. 



Tuesday, September 9, 2014

Function of the POLH gene...

The POLH gene provides instructions for making DNA polymerase eta. DNA polymerases are a group of enzymes which "read" sequences of DNA and use them as templates to produce new DNA. These enzymes play an important role in replication (copy) for cell division. DNA polymerase also play critical role in DNA repair.

The major function of DNA polymerase eta is to replicate damaged DNA from ultraviolet (UV) rays. Other DNA polymerases are unable to replicate DNA with the damage caused by ultra violet rays. When they reach a segment of damaged DNA, they get stuck and the replication process stalls. However, when DNA polymerase eta encounters damaged DNA, it skips over the abnormal segment and continues copying. This ‘Translesion Synthesis’ activity allows cells to tolerate some abnormalities created by UV exposure. Without this tolerance, unrepaired DNA damage would block DNA replication causing the cell death. Therefore, DNA polymerase eta plays an essential role in protecting cells from some of the effects of DNA damage.


DNA polymerase eta is a relatively "error-prone" polymerase. When it bypasses damaged DNA, it often inserts an incorrect DNA building block (nucleotide). This type of error results in a mutation in the replicated DNA.



Tuesday, September 2, 2014

POLH gene … Location

Cytogenetic Location: 6p21.1
Molecular Location : Chromosome 6
base pairs 43,576,140 ~ 43,620,522





The POLH gene is located on the short (p) arm of chromosome 6 at position 21.1, precisely from base pair 43,576,140 to base pair 43,620,522.


Monday, September 1, 2014

POLH gene … Official name

Official Name: polymerase (DNA directed), eta.
Official Symbol: POLH 
Other Names:
Ê DNA polymerase eta
Ê FLJ16395
Ê FLJ21978
Ê POLH_HUMAN
Ê RAD30
Ê RAD30A
Ê RAD30 homolog A
Ê xeroderma pigmentosum variant type protein
Ê XPV

Ê XP-V


Wednesday, August 27, 2014

How mutations in ERCC3 gene cause XP?

A single mutation in the ERCC3 gene causes Xeroderma Pigmentosum (XP). The mutation replaces the amino acid phenylalanine with the amino acid serine at protein position 99 (written as Phe99Ser or F99S) which greatly reduces the ability of the TFIIH complex to repair damaged DNA. As a result, abnormalities accumulate in DNA causing cells to malfunction and eventually become cancerous or die. These problems with DNA repair process cause people with XP to be extremely sensitive to UV rays from sunlight. When UV rays damage genes that control cell growth and division, cells can grow uncontrollably too fast, increasing the risk of developing cancer in XP patient. These cancers occur most frequently in areas of the body which are exposed to the sun such as the skin and eyes.

In addition to sun sensitivity, XP is sometimes associated with progressive neurological abnormalities but in affected individuals with Phe99Ser mutation have mild neurological abnormalities including hearing loss and poor coordination. Studies suggest that the neurological abnormalities associated with this condition result from a buildup of DNA damage, though the brain is not exposed to UV rays. Researchers suspect that other factors can damage DNA in nerve cells. It is unclear why some people with XP develop neurological abnormalities and others do not.


Monday, August 25, 2014

Normal function of the XPB/ERCC3 gene

The ERCC3 gene helps in making a protein called XPB. XPB is an essential subunit of a group of proteins known as the general transcription factor IIH (TFIIH) complex. The TFIIH complex has two major functions:

          I.      It involves in a process of gene transcription
        II.      It helps repair damaged DNA.

Gene transcription is the first step in protein production. By controlling gene transcription, the TFIIH complex helps regulate the activity of many different genes. Research suggest that the XPB protein works together with XPD, another protein in the TFIIH complex that is produced from the ERCC2 gene, to initiate gene transcription.

The TFIIH complex also plays an important role in repairing damaged DNA, which can be damaged by ultraviolet (UV) rays from the sun and by toxic chemicals, radiation and unstable molecules called free radicals. As we already know that DNA damage occurs frequently, but normal cells usually fix the damage through nucleotide excision repair (NER) mechanism before it can cause problems. As part of this repair mechanism, the TFIIH complex unwinds the section of double-stranded DNA that surrounds the damage. Studies suggest that the XPB protein may act as a wedge, holding open the two strands of DNA so other proteins can snip out (excise) the abnormal section and replace the damaged area with the correct DNA.




Tuesday, August 19, 2014

XPB/ERCC3 … Location

Cytogenetic Location: 2q21
Molecular Location: Chromosome 2
                           base pairs 127,257,289 ~ 127,294,175



The ERCC3 gene is located on the long (q) arm of chromosome 2 at position 21 from base pair 127,257,289 to 127,294,175 


Sunday, August 17, 2014

XPB/ERCC3 ..... Official Name

Official Name: excision repair cross-complementation group 3
Official Symbol: ERCC3
Other Names:
Ê  basic transcription factor 2 89 kDa subunit
Ê  BTF2
Ê  BTF2 p89
Ê  DNA excision repair protein ERCC-3
Ê  DNA repair protein complementing XP-B cells
Ê  ERCC3_HUMAN
Ê  excision repair cross-complementing rodent repair deficiency, complementation group 3
Ê  excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)
Ê  GTF2H
Ê  RAD25
Ê  TFIIH 89 kDa subunit
Ê  TFIIH basal transcription factor complex 89 kDa subunit
Ê  TFIIH basal transcription factor complex helicase XPB subunit
Ê  TFIIH p89
Ê  xeroderma pigmentosum, complementation group B
Ê  xeroderma pigmentosum group B-complementing protein
Ê  XPB


Sunday, August 10, 2014

How XPD/ ERCC2 cause XP .....

More than 24 mutations in the XPD/ERCC2 gene have been identified in people with Xeroderma Pigmentosum (XP). In USA, mutations in XPD gene are the second most common cause of XP.

The XPD/ERCC2 gene mutations prevent the TFIIH complex from repairing damaged DNA effectively. As a result, abnormalities accumulate in DNA, causing cells to malfunction and eventually the cells become cancerous or die. These problems with DNA repair cause people with XP to be extremely sensitive to UV rays from sunlight. When UV rays damage genes which control cell growth and division, cells can grow too fast and in an uncontrolled way. As a result, people with XP have a greatly increased risk of developing cancer. These cancers occur most frequently in areas of the body exposed to the sun such as the skin and eyes.

When XP is caused by XPD/ERCC2 gene mutations, it is often associated with progressive neurological abnormalities such as hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing & talking, seizures etc. The neurological abnormalities are thought to result from a buildup of DNA damage, although the brain is not exposed to UV rays. Researchers suspect that other factors damage DNA in nerve cells. It is unclear why some people with XP develop neurological abnormalities while others do not.




Monday, August 4, 2014

Normal function of the XPD / ERCC2 gene

The ERCC2 gene provides instructions for making a protein called XPD. This protein is an essential subunit of a group of proteins known as the general transcription factor IIH (TFIIH) complex. The TFIIH complex has two major functions:

1) It is involved in a process called gene transcription
2) It helps repairing damaged DNA.

Gene transcription is the first step in protein production. By controlling gene transcription, the TFIIH complex helps regulate the activity of many different genes. The XPD protein appears to stabilize the TFIIH complex. Studies suggest that the XPD protein works together with XPB, another protein in the TFIIH complex that is produced from the ERCC3 gene, to initiate gene transcription.

The TFIIH complex also plays an important role in repairing damaged DNA, which can be damaged by ultraviolet (UV) rays from the sun and by toxic chemicals, radiation, and unstable molecules called free radicals. DNA damage occurs frequently but normal cells are usually able to fix it before it can cause problems ¾ with the help of nucleotide excision repair (NER) mechanism. As part of this repair mechanism, the TFIIH complex separates the section of double-stranded DNA which surrounds the damage. The XPD protein helps with this process by acting as a helicase, which is an enzyme that attaches to particular regions of DNA and temporarily unwinds the two spiral strands. Once the damaged region has been exposed, other proteins excise the abnormal section and replace the damaged area with the correct DNA.


Friday, August 1, 2014

XPD/ ERCC2 ... Location

Cytogenetic Location: 19q13.3
Molecular Location: Chromosome 19
                           base pairs 45,351,390 ~ 45,370,586

   


The XPD/ ERCC2 gene is located on the long (q) arm of chromosome 19 at position 13.3 from base pair 45,351,390 ~ 45,370,586.


Thursday, July 31, 2014

XPD / ERCC2 ..... Official Name

Official Name:  Excision repair cross-complementation group 2
Official Symbol: ERCC2 
Other Names:
Ê basic transcription factor 2 80 kDa subunit
Ê BTF2 p80
Ê COFS2
Ê CXPD
Ê DNA excision repair protein ERCC-2
Ê DNA repair protein complementing XP-D cells
Ê EM9
Ê ERCC2_HUMAN
Ê excision repair cross-complementing rodent repair deficiency, complementation group 2
Ê MAG
Ê MGC102762
Ê MGC126218
Ê MGC126219
Ê TFIIH
Ê TFIIH 80 kDa subunit
Ê TFIIH basal transcription factor complex 80 kDa subunit
Ê TFIIH basal transcription factor complex helicase subunit
Ê TFIIH p80
Ê TTD
Ê xeroderma pigmentosum complementary group D
Ê xeroderma pigmentosum group D-complementing protein

Ê XPD