Monday, December 30, 2013

Mutations in the WNT3 gene cause TAS

A mutation in the WNT3 gene has been shown to cause Tetra-Amelia Syndrome [TAS] among members of one large family from Turkey. This mutation, which occurs in both copies of the WNT3 gene in each cell, replaces one protein building block (amino acid) with a premature stop signal in the instructions for making the WNT3 protein. This mutation is written as ‘Gln83Ter or Q83X’.

Researchers believe that the Gln83Ter mutation results in the production of an abnormally short, nonfunctional version of the WNT3 protein. Loss of the WNT3 protein disrupts normal limb formation before birth and leads to the other serious birth defects associated with Tetra-Amelia Syndrome [TAS].

Sunday, December 29, 2013

Normal Function of WNT3 gene .....

The WNT3 gene is part of a large family of WNT genes, which play critical roles in development before birth. WNT genes provide instructions for making proteins that participate in chemical signaling pathways in the body. These pathways control the activity of certain genes and regulate the interactions between cells during embryonic development.

Research in animals indicates that the protein produced from the WNT3 gene is critical for the outgrowth of the limbs in the developing embryo. The WNT3 protein also appears to play an important role in determining the anterior-posterior axis (the imaginary line that runs from head to tail in animals) during the earliest stages of embryonic development. Additionally, the effects of mutations in the human WNT3 gene suggest that the protein may be involved in the normal formation of the facial features, head, heart, lungs, nervous system, skeleton, and genitalia.

Saturday, December 28, 2013

WNT3 gene share characteristics with other genes

The WNT3 gene belongs to a family of genes called ‘Endogenous Ligands’. It also belongs to a family of genes called WNT (wingless-type MMTV integration site family).

Friday, December 20, 2013

WNT3 Gene ...... Location

Cytogenetic Location: 17q21
Molecular Location: Chromosome 17
Base pairs (bp) 44,839,871 ~ 44,896,125

The WNT3 gene is located on the long (q) arm of chromosome 17 at position 21.

The WNT3 gene is located on the long (q) arm of chromosome 17 at position 21, more precisely from bp 44,839,871 ~ 44,896,125.

Thursday, December 19, 2013

The Gene …… WNT3

Official Name: wingless-type MMTV integration site family, member 3

Official Symbol: WNT3 

Other Names:
·       INT4
·       Oncogene INT4
·       Proto-oncogene protein Wnt-3
·       WNT3_HUMAN
·       WNT-3 proto-oncogene protein

Wednesday, December 18, 2013

Gene .....

From one large family of affedted Tetra Amelis Syndrome [TAS] researcher found mutation in the WNT3 Gene.

WNT3 gene is part of a family of WNT genes which play critical roles in development before birth.

The protein produced from the WNT3 gene is involved in the formation of the limbs and other body systems during embryonic development.

Mutations in the WNT3 gene prevent cells from producing functional WNT3 protein which disrupts normal formation of limb and leads to the other serious birth defects associated with Tetra Amelia Syndrome [TAS].

In other affected families, the cause of Tetra Amelia Syndrome [TAS] has not been determined. Researchers believe that unidentified mutations in WNT3 or other genes involved in the development of limb are probably the reason behind this Tetra Amelia Syndrome [TAS].

Then mutation detection frequency is unknown as only a limited number of families have been studied.

Tuesday, December 17, 2013

Diagnosis .....

Clinical Diagnosis

Tetra Amelia Syndrome [TAS] is characterized by the complete absence of all four limbs (Figure 1). The diagnosis of Tetra Amelia Syndrome can be established clinically and is usually made on routine Prenatal Ultrasonography (Figure 2).

Figure 1

Figure 1. Postmortem radiograph of fetus with tetra-amelia syndrome demonstrating absence of all four limbs (without defects of scapulae and clavicles)

Figure 2

Figure 2. Prenatal ultrasonography showing fetus without limbs


Cytogenetic analyses, performed in some of the reported cases, showed normal karyotypes without ‘premature centromere separation’ (Roberts syndrome:

Molecular Genetic Testing

Gene: WNT3 is the only gene in which mutations are known to cause Tetra Amelia Syndrome [TAS] in one family [Niemann et al 2004].

Evidence for Locus Heterogeneity: Genetic heterogeneity of Tetra Amelia Syndrome [TAS] is strongly suggested by Krahn et al [2005]& Sousa et al [2008], who described fetuses with tetra-amelia, agenesis of both lungs, cleft lip/cleft palate and micrognathia in whom no mutations were identified in the coding exon regions of WNT3 and other candidate genes.

Clinical Testing

Summary of Molecular Genetic Testing Used in Tetra-Amelia Syndrome

Gene Symbol
Test Method
Mutations Detected
Mutation Detection Frequency by Test Method 1
Test Availability
Sequence analysis
(c.247C>T) 2
Unknown 3
Deletion/ Duplication Analysis 4
Deletion/Duplication of one or more ‘exons’ or the whole gene
none reported 5

1. The ability of the test method used to detect a mutation that is present in the indicated gene
2. Only one family studied to date [Niemann et al 2004]
3. Percentage of detectable mutations is unknown, as a WNT3 mutation has so far been demonstrated in only one family with tetra-amelia syndrome [Niemann et al 2004].
4. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), andchromosomal microarray (CMA) that includes this gene/chromosome segment.

5. No deletions or duplications of WNT3 have been reported to cause tetra-amelia syndrome. (Note: By definition, deletion/duplication analysis identifies rearrangements that are not identifiable by sequence analysis of genomic DNA.)

Friday, December 13, 2013

Symptoms ....

Tetra Amelia Syndrome [TAS] is characterized by the complete absence of all 4 limbs and following anomalies may involve:

Cranium & Face
      Cleft Lip/Cleft Palate
      Single Naris
      Choanal Atresia
      Absence Of Nose
      Palpebral Fusion
Urogenital System
      Renal Agenesis
      Persistence Of Cloaca
      Absence Of External Genitalia
      Atresia Of Vagina

Anus: Atresia
Lungs: Hypoplasia/aplasia
      Hypoplasia/absence of pelvic bones
      Absence of ribs, absence of vertebrae
 Central nervous system
      Agenesis Of Olfactory Nerves,
      Agenesis Of Optic Nerves
      Agenesis Of Corpus Callosum

As we discussed earlier the affected infants are often stillborn or die shortly after birth.

Thursday, December 12, 2013

Inheritance ……

Tetra-amelia syndrome is inherited in an autosomal recessive manner’. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with tetra-amelia syndrome each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes (carriers) are asymptomatic. 

Wednesday, December 11, 2013

How common is Tetra-Amelia Syndrome?

Tetra-Amelia Syndrome is an extremely rare disorder and has been described in only 5 families of different ethnic backgrounds (Arab, Morocco, Syrian-Aramatic, Australia, Japan) till date.

So far 2 famous personalities have survived Tetra Amelia Syndrome (TAS):

1.  Nicholas (Nick) Vujicic [Motivational Speaker]
2.  Hirotada Ototake [Japanese Author & Sports Journalist]

Tuesday, December 10, 2013

Tetra-Amelia Syndrome ... What is it ???

Tetra-Amelia Syndrome (TAS) is a very rare disorder characterized by the absence of all the four limbs.

‘Tetra’ is a Greek word for ‘Four’
‘Amelia’ refers to the failure of development of an arm/leg before birth.

TAS can also cause severe malformations of other parts of the body including the head & face, heart, nervous system, skeleton, and genitalia.

The lungs are underdeveloped in many cases which makes breathing difficult or impossible.

Most of the children with Tetra-Amelia Syndrome (TAS), having such serious medical problems, are stillborn or die shortly after birth.

Monday, December 9, 2013

Life Without Limbs ... Tetra Amelia Syndrome

Imagine being born without hands !!! No arms to hug your loved one, wrap around a friend ¾ no fingers to experience touch ¾ no way to lift or carry things.

Picture your life without the ability to walk, run or even stand in your two feet.

Now put both the scenario together ¾ No Arms … No Legs ……… Perplexed !!!

How much more difficult would life be if you were living without arms or legs? What would you do? How would that affect your everyday life?

In my last video meet Mr. Nick Vujicic (pronounced ‘Vooy-cheech), born in 1982 in Brisbane, Australia, without any medical explanation or warning, Nicholas Vujicic came into the world with neither arms nor legs. Imagine the shock his parents felt when they saw their first-born brand new baby boy for the first time, only to find he was what the world would consider abnormal. 

Nick was born with Tetra-Amelia Syndrome where the arms & legs were not developed at all !!!

Thursday, October 24, 2013

Thank You Readers for let me achieve 30,000 views!

Keep Reading to engross yourself!

Saturday, September 21, 2013

Stages & Effects

There are four stages of Fatal Familial disorder (FFI):

Stage One: (typically 4 months): the 1st stage includes sudden onset of sleepiness and insomnia resulting in phobias, paranoia and panic attacks.

Stage Two: (typically 5 months): During the 2nd stage hallucinations and panic attacks become increasingly apparent.

Stage Three: (typically 3 months or more): This stage includes the absolute inability to sleep along with rapid weight loss and diminished cognitive performance.

Stage Four: (Typically lasts for 6 months): The end stage includes ‘dementia’. The patient becomes mute and unresponsive over the course of 6 months after which death occurs.

Writing in a 2006 issue of the Medscape General Medicine journal, Dr. Joyce Schenkein outlined the etiology and characteristics of FFI. She noted that it often begins in middle age (average age of onset being 50 years) and has no cure (even ‘gene therapy has been unsuccessful to date). Unfortunately, the prognosis following initial diagnosis is poor with FFI sufferers’ only living for an average of about a year and a half (with Dr. Schenkein noting that survival ranged from 7 to 36 months from diagnosis of FFI). It originates in the form of unexplained sleeplessness before rapidly developing into a fatal insomnia. 

Further Reading:
Schenkein, J. (2006). Self-management of fatal familial insomnia. Part 1: What Is FFI? Medscape General Medicine, 8(3), 65.
Schenkein, J. & Montagna, P (2006). Self-management of fatal familial insomnia. Part 2: Case report. Medscape General Medicine, 8(3), 66.

Sunday, September 15, 2013

History ...

Knowledge of Fatal Familial Insomnia (FFI) is recent — discovered only in the early 1990’s and the credit goes to Dr. Ignazio Roiter for his role in uncovering this very rare disease. Dr. Ignazio Roiter is a specialist in internal medicine & endocrinology and is head physician of the Treviso Hospital, Italy.

The family of Dr. Ignazio’s wife Elisabetta carries the fatal gene. Elisabetta has been losing a family member every 3 years. These inexplicable deaths after months of sleeplessness drew the attention of Bologna experts. It was at a meeting held in the Dr. Ignazio’ living room where Elisabetta, Dr. Ignazio and Bologna researchers agreed to call the disease Fatal Familial Insomnia (FFI). Due to the series of deaths their family went through, Dr. Ignazio and Elisabetta made it their mission to create a detailed family tree. Centuries of records of births and deaths of people in a parish in Veneto, northern Italy provided the basic information for the family tree project. However, it took a special skill to gain access to parish records. Ignazio who plays the organ as a hobby, performed for the aged priest of the parish church. In gratitude of the musical treat, the priest gave Ignazio access to the parish’s old records. Ignazio traced the appearance of fatal familial insomnia (FFI) in Elisabetta’s family in the 17th century. 250 years ago, a wealthy Venetian doctor carried the genetic mutation. He was referred to as patient zero, the first known case.

This man suffered from insomnia for more than a year and spent his last months paralyzed by exhaustion until he died in 1765. This started a chain and his descendants were recorded to have experienced never-ending sleeplessness in the 18th and 19th century — eventually succumbing to varied side effects as heart problems, encephalitis and pellagra. The doctor’s descendants showed symptoms of sweating, fever, hallucinations, insomnia and, in one case of possession.

Wednesday, September 11, 2013

What is Fatal Familial Insomnia (FFI)?

Fatal Familial Insomnia (FFI) is an extremely rare inherited autosomal dominant disorder of brain — most often caused by a protein mutation passed on through families. But FFI can also develop spontaneously with a non-inherited mutation variant called Sporadic Fatal Insomnia (sFI).

FFI is clinically characterized by insomnia with/without a diurnal dreaming state, hallucinations, delirium and dysautonomia preceding motor and connective deterioration.

The average age of onset in FFI is 50 but can range from 18-60 years.

Worldwide there are only 40 families which have been found to carry the disease, affecting about 100 people altogether.

If the parent has the mutated gene there will be 50% chance that the child will also inherit the disease.

Monday, September 9, 2013

A Life without Dream !!!!!

Imagine what a nightmare it would be to never have a nightmare!!!

Imagine a life without a dream!!!

Imagine to be banished forever from the topsy-turvy realm of sleep!!!

One day you just wake up and never falls asleep again — tortured in a twilight world of perpetual insomnia — lying in the bed; exhausted but with eyes wide open — listing to the groans and whispers of the night — sleepless, until death mercifully claim you.

Sound like a Gothic Chiller???

Sleep is a mystery yet to be solved. Science still does not know why and how we do it. Now pioneering research takes us insight the sleeping brain and re examines a mind – forbidden to rest/which prohibit rest— Insomnia with a fatal twist — lack of sleep will kill you but science to figure out why???

We might not ever heard of this very rare, real genetic disorder — Fatal Familial Insomnia (FFI) — without the medical detective work of an Italian family, which in turn was stalked for centuries with a terrifying fate.

Wednesday, August 28, 2013

Thank you for your patience !

Hi Friends,
I became a little busy with my personal stuff, but now I am back in action J
Currently I am researching on a very strange disease. I will beck with that soon J

Till then thank you for your patience.

Thursday, August 1, 2013

How ADAMTS2 Gene Cause EDS?

Mutation in the ADAMTS2 gene is responsible for 'Dermatosparaxis Types' of Ehlers-Danlos syndrome (EDS). These mutations greatly reduce the production/activity of the enzyme made by the ADAMTS2 gene. 

Procollagens cannot be processed correctly without this enzyme. As a result, collagen fibrils are not assembled properly they appear ribbon-like and disorganized under the microscope. Cross-links, or chemical interactions, between collagen fibrils are also disrupted. These defects weaken connective tissue (the tissue that binds and supports the body's muscles, ligaments, organs, and skin), which leads to the signs and symptoms of the EDS.