Alport Foundation of Australia
 

Which genes are affected in Alport Syndrome?


Three subdivisions of Alport exist:


  1. (1)Autosomal Dominant Alport Syndrome (ADAS)

  2. Quite rare, about 5% of individuals with AS.


A mutated gene exists on one of the numbered chromosomes. There are two copies of every chromosome, and the dominant mutated gene will override the working gene. However, this form of the disease progresses more slowly than other forms.


  1. (2)Autosomal Recessive Alport Syndrome (ARAS)

  2. About 15% of individuals with AS.


A recessive mutated gene on an autosome will be overridden by a working gene. Thus, for the offspring to develop AS, they must receive a recessive mutated gene from both parents.  If an individual has only one mutated recessive gene, then he/she is a carrier of AS, but will not usually develop the disease. Both males and females are affected equally with ARAS and may develop end stage renal disease (ESRD) by the age of 30.


  1. (3)X Linked Alport Syndrome (XLAS)

  2. 80% of individuals with AS.


This occurs when there is a mutated gene carried on the X (female sex) chromosome. This is why the disease is more severe in men (XY) than in women (XX), as generally females have one “good” X chromosome (from their father) to protect them and one with XLAS (form their mother). Male (XY) sufferers have only the one X chromosome, which is XLAS (from their mother). The Y chromosome is inherited from their father.  X linked Alport syndrome progresses more rapidly in males, with end stage renal disease (ESRD) usually occurring in males between the ages of 30 and 50.







Transfer Rules for XLAS (X linked) to Next Generation:


Fathers pass a copy of their Y (male) chromosome to their sons. Thus sons of male XLAS sufferers have 0% chance of inheriting XLAS.  Fathers pass a copy of their X (female) chromosome to their daughters. Thus, ALL daughters of a male with X linked Alport syndrome (XLAS) will have a 100% chance of inheriting the disease.


All sons and daughters of a woman carrying Alport syndrome (XLAS) have a 50% chance of receiving their mother’s mutated XLAS chromosome, as the mother will always pass on one of her two X chromosomes (X, or the mutated XLAS).


HOW X-LINKED ‘AS’ IS INHERITED FROM XLAS FATHER

   Parents

                                                                Unaffected mother XX   XY Affected father (his X goes to daughters Y goes to sons)

Daughters        Sons

        All his daughters will inherit his XLAS XX or XX      XY or XY none of his sons will inherit the disease



HOW X-LINKED ‘AS’ IS INHERITED FROM XLAS MOTHER

    Parents

                                                                         Affected mother XX   XY Unaffected father (his X goes to daughters Y goes to sons)

Daughters        Sons

There is a 50% chance her daughters will inherit her XLAS XX or XX       XY or XY There is a 50% chance her sons will inherit her XLAS


X = mutated XLAS


Why is it important to locate Alport sufferers?


An Alport carrier may be unaware of any problem, even at age 30. By then the mutation may have been passed on to the next generation. However, if we know that certain family members have XLAS then it is possible potentially to determine who in the family tree is at risk. Finding other living family members who may unknowingly have Alport Syndrome will benefit those people in two ways: firstly by early detection (a simple urine and blood test is a good start) treatment could be started much sooner, giving them better health outcomes and secondly, they may choose to discuss with their doctors or a geneticist the possibility of eliminating the disease from their descendants.


Treatment of Alport Syndrome


At present there is no cure for Alport Syndrome. Certain blood pressure lowering medications are known to also decrease the amount of protein leakage from the kidneys.  Other medications may also be prescribed for individuals who exhibit further complications. The current aim of treatment is to slow the progress of the disease.


Hearing aids and lens replacement of the eye may be required in the treatment of some Alport sufferers. A healthy diet consisting of low salt and low protein is usually recommended in order to ease the pressures on the kidney. When kidney failure occurs dialysis is recommended, or transplantation may be an option for the patient.


There is well deserved optimism that current research will lead to reversal/cure.  It is early days for this, but when something comes through it is most important to find people who can benefit from current developments.  See for example this project:


Some Informative Articles:


SPECIAL ARTICLE

Expert Guidelines for the Management of AS


There are many articles on XLAS, e.g. “Hereditary_nephritis_-_Alport_Syndrome.pdf” available here:

http://www.kidney.org.au/PatientInformation/HealthFactSheets/tabid/609/ItemId/292/Default.aspx

Also see:

“Winding Back the Clock with Kidney Stem Cells” - Dr Sharon Ricardo

http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling/Alport_Syndrome#Support_groups

WHAT IS ALPORT SYNDROME ?
View  movie presentations about  Alport SyndromeDR_PARKIN_MOVIE.htmlshapeimage_5_link_0

Alport Syndrome is a hereditary kidney disease, (sometimes referred to as hereditary nephritis) which eventually causes renal failure and sometimes other symptoms, such as deafness and eye abnormalities (lenticonus).


Symptoms of Alport Syndrome include blood in the urine (may not be visible), protein in the urine (trace to large amounts), high blood pressure, possible deafness and possible vision problems. The degree of symptoms varies between families and also between sexes, as female sufferers may have very mild symptoms. The outcome for males is usually more severe, with 90% of males suffering renal failure by the age of forty.


If anyone in your family is diagnosed with Alport Syndrome it is vital that all members of the family, male and female, investigate the possibility that they too have inherited the disease. Genetic counselling is recommended.


Why are the kidneys, ears and eyes affected in Alport Syndrome?


Firstly we need to understand that the body is held together by connective tissue and this connective tissue is made up of “collagen”, which itself consists of strands of proteins assembled like the strands in a rope. There are many “types “of collagen throughout the body, and type IV collagen is found only in basement membranes of the glomerulus (the filter) of the kidney, the cochlea of the ear and the lens of the eye.


Specific genes carry the information (or pattern) for the “knitting together” of the strands of protein to form collagen.  Hence any mutation in a “type IV” pattern carrying gene will have the potential to affect the ear, the eye and the kidney. The most serious problems arise from impairment of the glomerulus of the kidney.

ALPORT SYNDROME BACKGROUND

The Alport Support Group Inaugural Meeting 

was held in September, 2009 
 Northern Hospital, Epping, Victoria.

View  movie presentations of the meetingDR_PARKIN_MOVIE.html
Alport Syndrome Symposium 

was held in New York, August 2010.
Elizabeth & David Blatt attended the symposium 
on behalf of the
 ALPORT FOUNDATION OF AUSTRALIA 

Click here to view
Feedback from this eventhttp://www.alportsyndrome.org/about-alport-syndrome/announcements/new-york-announcement-letter/shapeimage_9_link_0
 Dr Alison Blatt spoke at the launch of
Genetic Awareness Week
15th September, 2010. 

Click here to view Alison’s presentation
:
Click here to read Alison’s 
recount of how PGD IVF enabled 
her to have a disease free childDR_BLATT_MOVIE.htmlGENETIC_AWARENESS.htmlGENETIC_AWARENESS.htmlGENETIC_AWARENESS.htmlshapeimage_10_link_0shapeimage_10_link_1shapeimage_10_link_2shapeimage_10_link_3


The Alport Syndrome Foundation in USA hosted the 

Alport Syndrome Symposium for Physicians, Researchers, & Families

This event was attended by representatives of the ALPORT FOUNDATION of AUSTRALIA, in New York.

Information and feedback about the symposium is published on the website of the Alport Syndrome Foundation (USA) 


SPECIAL ARTICLE:

Expert Guidelines for the Management of Alport Syndrome and Thin Basement Membrane Nephropathy

18 recommendations for the diagnosis, management and treatment of AS

Published August 2013 by

Judy Savige, Martin Gregory,  Oliver Gross,  Clifford Kashtan, Jie Ding,  and Frances Flinter






READ THE ABSTRACT OR DOWNLOAD THE ENTIRE ARTICLE  AND THE 18 RECOMMENDATIONS IN DETAIL
 pdf formatAWARENESS_files/Expert%20guidelines%20for%20AS.pdf

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