Dec 282012
 

At the Nystagmus Network Open Day, a speaker on genetics explained that with nystagmus the most common genetic pattern is X linked, but it can also be autosomal recessive or autosomal dominant.  It made us curious to find out more about our situation and this post explains what we’ve learned …   

We first needed to understand what these terms meant so (not remembering much from GCSE Science) we googled!


Introduction to genetics

We inherit a set of genes (instructions) from both our parents.  Genes can either be found within our sex chomosomes (we have one pair each – females have XX, males have XY) or within our autosomal chomosomes (we have 22 pairs of non-sex chromosomes).  If a genetic pattern is X linked the faulty gene lies on the X sex chromosome.  If the genetic pattern is autosomal, it lies on one of the 22 pairs of non-sex chromosomes.

If a faulty gene is dominant it is capbable of causing disease, even where a matching gene from the other parent is normal.  If it is recessive, in most cases, both matching genes (one from each parent) must be faulty to cause disease.  This is because it’s usually possible for the body to use the instruction from the normal gene if only one is faulty.

We found some very helpful and more detailed information within these three leaflets on the Genetics Alliance website which we highly recommend reading.

1) X linked inheritance
2) Recessive Inheritance
3) Dominant Inheritance


Genetics and Albinism

From the Noah (National Organization for Albinism and Hypopigmenation) website we’ve learned the inheritance patterns for albinism differ depending on the type.

If Jack has Ocular Albinism, which primarily involves lack of pigment in the eyes (although hair and skin may appear similar or slightly lighter than that of other family members), it’s likely the inheritance pattern will be X linked.

The Noah website says :

“In most cases ocular albinism is X-linked, which means the gene for it is on the X chromosome. X-linked ocular albinism occurs almost exclusively in males. It is passed from mothers who carry the gene to their sons. Each time a mother who carries the gene for ocular albinism gives birth to a son, there is a 1 in 2 chance that the son will have ocular albinism. Mothers who carry the gene may have mottled pigmentation in the back of their eyes, but do not have the full syndrome of ocular albinism. An ophthalmologist may be able to identify this mottling in about 80% of cases.”

 (Source : http://www.albinism.org/publications/ocular.html)

It also says:

“Ocular albinism (OA1) is caused by a genetic defect of the GPR143 gene that plays a signaling role that is especially important to pigmentation in the eye. OA1 follows a simpler pattern of inheritance because the gene for OA1 is on the X chromosome. Females have two copies of the X chromosome while males have only one copy (and a Y chromosome that makes them male). To have ocular albinism, a male only needs to inherit one defective copy of the gene for ocular albinism from his carrier mother. Therefore almost all of the people with OA1 are males. Indeed, parents should be suspicious if a female child is said to have ocular albinism.”

(Source: http://www.albinism.org/publications/what_is_albinism.html)

If Jack has Oculocutaneous (pronounced ock-you-low-kew-TAIN-ee-us) albinism (OCA) which involves the eyes, hair and skin, it’s likely the inheritance pattern will be autosomal recessive.

The Noah website says:

“The genes for OCA are located on “autosomal” chromosomes. Autosomes are the chromosomes that contain genes for our general body characteristics, contrasted to the sex chromosomes. We normally have two copies of these chromosomes and the genes on them – one inherited from our father, the other inherited from our mother. Neither of these gene copies is functional in people with albinism. However, albinism is a “recessive trait”, so even if only one of the two copies of the OCA gene is functional, a person can make pigment, but will carry the albinism trait. Both parents must carry a defective OCA gene to have a child with albinism. When both parents carry the defective gene (and neither parent has albinism) there is a one in four chance at each pregnancy that the baby will be born with albinism. This type of inheritance is called “autosomal recessive” inheritance.”

(Source: http://www.albinism.org/publications/what_is_albinism.html)

It is possible the inheritance pattern for Ocular Albinism can be autosomal recessive too, although research suggests that autosomal recessive ocular albinism is a variant of oculocutaneous albinism.


The next generation and beyond …

One of the things we were most keen to learn as part of this research was what are the chances of Jack passing on nystagmus/albinism to his children.

For X linked we learned if Jack has sons, they will be unaffected (they won’t have the condition and they won’t be carriers).  If he has daughters, each of them will be a carrier, but won’t have the condition themselves.

Jack’s daughters, as for myself (Mum) as a carrier, would have a 50% chance of passing the condition to each of their son’s, and there would be a 50% chance that each of their daughters will be carriers.

For autosomal recessive, we learned that Jack would have to have children with another carrier of the same gene defect as him to have an affected child – so the chances would be slim.  If his partner is not a carrier, their “good” gene instruction should override Jack’s bad gene one.

Please refer to the attached Genetics Alliance leaflets (see 1) and 2) in the Introduction section above) for diagrams and further explanation.


Gentics testing

If you’d like to find out more about genetics testing the speaker at the Nystagmus Network Open Day recommended speaking to your Opthamologist.

In the UK, there are 20 specialist genetics units which can help you find out more about where nystagmus/albinism may have come from and the chances of passing it to future generations.  Our closest is the Institute of Genetic Medicine at the Centre for Life in Newcastle.  A UK wide list is available on the Genetic Alliance UK website here.

In the USA, the Noah Website recommends seeking out a qualified Geneticist or Genetic Counselor from either the American College of Medical Geneitcs or the National Society of Genetic Counselors referral lists.

In the USA, I’ve also recently learned of ongoing clinical trials for Oculocutaneous Albinism at the  National Institute of Health (NIH) Clinical Centre.  Here’s a summary of the purpose of their work from their website:

“First, we want to clinically and comprehensively characterize OCA subtypes, especially OCA-1 and OCA-2, with respect to the degree of hypopigmentation, genetic mutations, and extent of ocular involvement. Second, we plan to study patients’ cultured melanocytes for variability in pigment formation related to genotype, and test treatments to increase pigmentation. Third, we expect to ascertain rare patients with hypopigmentation not due to known albinism-causing genes. Finally, we will acquire sufficient experience in the care of patients with albinism to become experts in this disorder. This expertise will be especially valuable for potential future clinical trials. We will clinically evaluate patients of all ethnicities; obtain cells, plasma and urine for future studies; perform mutation analysis on known OCA causing genes; and search for other genes responsible for OCA. Routine admissions will last 4-5 days and occur every two years.”

It sounds a great way to get a more detailed diagnosis of the type of albinism (for those who don’t yet have one) as well as take part in vital research to help make a difference for the future.  I understand funding (including overnight accommodation) is available.  I wish we lived closer to Bethesta, Maryland where it’s located!  You can find out more here.


Summary

It’s taken a while to get our heads round this new information but we’re pleased we know more and are looking forward to getting the results from the genetic testing we’ve had done at Leicester as soon as they are available.  It’s been comforting to learn that the chances of Jack passing on the condition to his children and future generations is lower than what we first thought.  We’d love to hear from you about any genetics related experiences.

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