ATP6V0A2 Gene …… Location

Cytogenetic Location: 12q24.31

Molecular Location: Base pairs 123,712,317 ~ 123,761,754 on chromosome 12

The ATP6V0A2 gene is located on the long (q) arm of chromosome 12 at position 24.31, precisely from the base pair 123,712,317 to base pair 123,761,754.

Source: www.ghr.nlm.nih.gov

ATP6V0A2 Gene ... Official Name

Official Name: ‘ATPase, H+ transporting, lysosomal V0 subunit a2’

Official symbol: ATP6V0A2 

The ATP6V0A2 gene is also known by the following name:

E  A2V-ATPase

E  ATP6a2

E  ATP6N1D

E  J6B7

E  Stv1

E  TJ6

E  TJ6M

E  TJ6s

E  Vph1

E  VPP2_HUMAN

Source: www.ghr.nlm.nih.gov

Genes…… (2/2)

Most of the genes are the elements of fibers ¾ slender bundle of protein provide strength and flexibility to connective tissue throughout the body. Elastic fibers allow the skin to stretch ¾ the lungs to expand & contract and arteries to handle the pressure of blood flow.

The major component of elastic fibers ¾ Elastin ¾ is produced from ELN gene. Other critical proteins of elastic fibers are produced by the following genes:

E EFEMP2

E FBLN5

E ATP6V0A2 

Mutations in any of these gene hamper the formation, assembly or function of elastic fibers.

Now, a shortfall in elastic fibers weakens connective tissue in the skin, arteries, lungs and other organs. These mutations in connective tissue cause the major feature of ‘Cutis Laxa’ to a small percentage. Researcher suspects that mutation in other genes, which is yet to identify may also be responsible for Cutis Laxa.

The chances of Acquired Cutis Laxa (ACL) are very rare. Acquired Cutis Laxa (ACL) is caused by the destruction of normal elastic fibers and not by inheritance. Though the causes of ACL are unclear, but it may occur due to the side effect any medical treatment which remove copper from body.

Source: www.ghr.nlm.nih.gov

Genes…… (1/2)

Cutis Laxa is caused by the mutation in the following genes:

E ATP6V0A2

E ATP7A

E EFEMP2

E ELN/FBLN5

Inheritance .....

Most of the cases Cutis Laxa is inherited. There generally 3 types of forms of genetic inheritance…

E Sex Linked

E Autosomal Dominant

E Autosomal Recessive

The Autosomal Recessive form is the most common & severe.

Sex-linked	The defective/mutated gene is carried on one of the sex chromosomes, in this case it is located on the X chromosome
Autosomal Dominant	Only one copy of the defective/mutated gene is enough to cause CL. A child has a 50% chance of inheriting the gene from either parent.
Autosomal Recessive	In this type the affected child must inherit two copies of the defective/mutated gene from both of its parent. The chance of transmitting an autosomal recessive disease is 25% for each pregnancy.

History .....

Historically, Cutis Laxa (CL) was often confused with EDS (Ehlers Danlos syndrome), until 1923, when E. Parkes Weber noted the clinical differences between these two condition.

The internal involvement and the systemic nature of CL were elucidated by Goltz and co-workers, who emphasized the phenomenon of generalized elastolysis in same patient.

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.

The Name .....

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

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.

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.

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

Photo courtesy: http://niewiarygodne.pl/gid,15060287,img,15060343,kat,1017185,title,Przerazajaca-choroba-Ta-babcia-ma-18-miesiecy,galeriazdjecie.html

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 ??

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.

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

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.

 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.

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 with her Birth Certificate

Photo courtesy: www.mirror.co.uk/tv/tv-news/zara-hartshorn-familys-battle-rare-1143344

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

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. 

Source: www.ghr.nlm.nih.gov

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.

Source: www.ghr.nlm.nih.gov

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.

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

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.

Source: www.ghr.nlm.nih.gov