Is a genetic test necessary for Lowe syndrome?

[fluidistic]

The sister of my girlfriend gave birth to a baby suffering Lowe syndrom. The baby who is now a child of 5 years old had been diagnosticed by his symptoms (cataracts at birth, problems with his kidneys, mental problems+convulsions and more medical tests that I'm not aware of). Just to give you an idea about how the child is now: he doesn't say a word, doesn't look at you in your eyes (though he can see at least "light" since he moves his head toward sources of light), doesn't walk nor take objects with his hands, etc.
The mother had been told that there exist a genetical test that could be done in the USA (she's from Argentina) that costs 1000 dollars -too much for her- and could be a very accurate diagnostic. So she never did the genetical test, although absolutely all symptoms the child suffers are according to Lowe syndrom; even the photos and videos on the Internet of children with this symptoms are so similar to the child that it's hard to doubt about the diagnostic.
The problem is that my girlfriend might have the defectuous gene causing this syndrom, and she might eventually transmit it to our probable future child. I asked my mother in France to ask in the hospital if they can do a genetic test and apparently there's only 1 place in mi city, but the doctor who do the test needs the genetic profile of the child of the sister of my girlfriend. Because otherwise "she doesn't know what to look for". Unfortunately we do not have the genetic profile of this child nor we will get it.

I was wondering if it's absolutely needed in order to genetically test my girlfriend to have the genetic profile of the child. On wikipedia (I know it can't be trusted... but still...), one reads

Lowe syndrome is a "genetic" condition (i.e. occurs from birth, due to a gene mutation that may not have any family history, or may be hereditary) and affects mainly males. It is caused by a single defective gene (an alteration or "mutation") in a gene called OCRL1. Because of this defective gene, an essential enzyme called PIP2-5-phosphatase is not produced. This is the underlying cause of Lowe syndrome.
The gene has been mapped and the deficient enzyme has been identified, although its role is not fully understood. Today there is no correlation between the gene mutation, the level of enzyme deficienty and the symptoms. Other Syndromes such as Dents, may have almost identical mutations but while exhibiting some symptoms such as kidney disorders, do not have the enzyme deficiency or other symptoms such as cataracts.
Much research has taken place in the last few years, but the diagnosis is still largely clinical, based on cataracts at birth in both eyes and a kidney disorder, plus a positive test for the enzyme deficiency.

.
I don't really understand wheather they mean it's possible to do a genetical test or not.
My girlfriend is already 30 years old (I'm 24) and we're planning to have some baby in the next few years. Not knowing if we could do one is a bit painful.
I don't really know where to head now... what do you have to say?
P.S.:In Argentina, as far as we know, there's no way to get a genetical test even of the children suffering from Lowe syndrom. The diagnostic is 100% clinical. This information comes from the largest children's hospital in Buenos Aires (Garrahan's hospital).

 

[atyy]

Bolding below is mine.

http://ghr.nlm.nih.gov/condition/lowe-syndrome
"In some cases of Lowe syndrome, an affected male inherits the mutation from a mother who carries one altered copy of the OCRL gene. Other cases result from new mutations in the gene and occur in males with no history of the disorder in their family."

http://www.ncbi.nlm.nih.gov/books/NBK1480/
"Genetic counseling. Lowe syndrome is inherited in an X-linked manner. New mutations have been reported in 32% of affected males with Lowe syndrome. A high risk of germline mosaicism (4.5%) has been identified. When a mother is a carrier, each pregnancy has a 25% chance of resulting in an affected boy, a 25% chance of resulting in a carrier daughter, a 25% chance of resulting in an unaffected boy, and a 25% chance of resulting in a girl who is not a carrier. No affected male is known to have reproduced. Approximately 95% of carrier females over age 15 years have characteristic findings in the lens of the eye when the lens is evaluated by an experienced ophthalmologist through a dilated pupil with a slit-lamp with both direct and retroillumination. Prenatal testing is available. Assay of enzyme activity is the preferred method for prenatal diagnosis for Lowe syndrome. Molecular genetic testing may be used to confirm the enzymatic assay results if the OCRL mutation has been identified in an affected family member; however, such testing is not always necessary."

"Female carriers of Lowe syndrome. Approximately 95% of postpubertal carrier females have characteristic findings in the lens of each eye when the lens is evaluated through a dilated pupil with a slit-lamp by an experienced ophthalmologist. The lens findings have correlated with the results of molecular genetic studies in predicting carrier status of postpubertal females [Lin et al 1999, McSpadden 2000, Roschinger et al 2000, Nussbaum & Suchy 2001]. While the lens findings may be present in prepubertal females as well, especially the less common axial posterior central opacity, their absence does not exclude carrier status.

Most carrier females show numerous irregular, punctate, smooth, off-white (white to gray) opacities, present in the lens cortex, more in the anterior cortex than the posterior cortex and wrapping around the lens equator. Classically, the nucleus is spared. On retroillumination, the opacities are distributed in a radial, spoke-like pattern and can be relatively dense in a wedge shape comparable to an hour or two on the face of a clock, alternating with a similar-sized wedge with few to no opacities.

A few carriers (~10%) have a dense central precapsular dead-white cataract at the posterior pole of the lens that may be visually significant if it is large."

"Sequence analysis of the OCRL gene identifies mutations in approximately 95% of males with Lowe syndrome. There are no common mutations. Although a few mutations have been noted in more than one affected individual, most mutations are unique to a family. "

"Note: (1) Linkage analysis may be considered in families with only one affected male; however, the possibility of a new mutation in the affected family member makes interpretation challenging. (2) Germline mosaicism, which can confound studies that rely on linkage alone for carrier detection, has also been documented in Lowe syndrome [Satre et al 1999, Monnier et al 2000]."

http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2509

 

[Monique]

but the doctor who do the test needs the genetic profile of the child of the sister of my girlfriend. Because otherwise "she doesn't know what to look for". Unfortunately we do not have the genetic profile of this child nor we will get it.

I was wondering if it's absolutely needed in order to genetically test my girlfriend to have the genetic profile of the child. On wikipedia (I know it can't be trusted... but still...), one reads .

The doctor is right, by having the genetic information of the affected child she can look if the same genetic defect is present in a carrier. As mentioned, 95% of the cases are explained by the OCRL gene, 5% are not.

The doctor could still sequence the OCRL gene of a potential carrier and check for known genetic lesions that occur in literature descriptions of people with Lowe syndrome. There won't be 100% certainty, but it is better than nothing.

However, ask the doctor whether a DNA kit can be sent to the affected child. All that is needed is some DNA, so a cheek swab should be sufficient! This cheek swab can then be sent back to the hospital. Since it is important information for the carrier-test, I think they should make the effort to test the affected family member.

 

[fluidistic]

Ok thank you very much to both.
The doctor said it was absolutely necessary to have the DNA of the affected child. My mother said the doctor mentioned some method to collect the DNA and preserve it (I think she said a blood test) although I instantly thought of a cheek swab. The problem is that I don't think it's that easy to send a DNA sample from Argentina to France due to severe controls. Also the child lives about 400 km from where I am and he lives in a small town.
From what atyy describes, I'm very tempted to look for that eye-lens test. I'd personally be conformed with an around 95% accurate diagnostic. Of course a DNA test+lens test would be even better but the former is causing me (us in fact) too much trouble. Not to mention that the parents of the child are somehow traumatized and if there's some blood extraction involved we can already forget it.
So right now I'm thinking of the ophthalmologist test; doing it twice. Here in Argentina once and once I go to France with my girlfriend (within a year or less, probably). I'm willing to take the 5% risk.
I'll keep you up to date if I know something else.

 

[Moonbear]

If you're traveling to France, maybe you can hand-carry a cheek swab test if you can visit the kid before you leave. It won't have anything on it a toothbrush wouldn't have, so shouldn't be a problem to just pack in your luggage.

 

[fluidistic]

If you're traveling to France, maybe you can hand-carry a cheek swab test if you can visit the kid before you leave. It won't have anything on it a toothbrush wouldn't have, so shouldn't be a problem to just pack in your luggage.

You are definitely tempting me to try it. Maybe I could even send a normal postcard with the sample.
A few questions since I may visist the child in less than a month...
I pass a cotton swab inside the mouth of the child (on the cheeks) and I put the cotton swab inside a Ziploc-like bag, send this bag inside a postcard. Is that enough to perform a good quality DNA test?
Also I guess I must take extremely care not to contaminate the sample with any other DNA so I may use gloves, is this right?
Could cerumen also do the job (it's more visible than saliva)? I know it's "dirty" but if this work... why not.

 

[Moonbear]

Cerumen won't work. That's a secretion, not actual cells. You need cells with nuclei. See if you can get a proper test kit. Otherwise, you do risk contamination. If you can't get that, I'm not sure how valid it will be, but you can try getting sterile swabs. You just need to rub it along the inside of the cheek to pick up some cheek cells. Maybe you can call to the person in France who will do the testing and see what will work.

 

[fluidistic]

Cerumen won't work. That's a secretion, not actual cells. You need cells with nuclei. See if you can get a proper test kit. Otherwise, you do risk contamination. If you can't get that, I'm not sure how valid it will be, but you can try getting sterile swabs. You just need to rub it along the inside of the cheek to pick up some cheek cells. Maybe you can call to the person in France who will do the testing and see what will work.

Ah I see. Before asking the doctor in France, what do you think about some hairs with their roots (bulbs)?