Prenatal Diagnosis - Science topic

Cheers Rezvan Marjani

You too!

Definitely no

First part of Jason's answer is correct, but the offspring carrying both traits would not suffer from severe anaemia and would be perfectly fine! He would have 1 functional beta gene and 3 functional aplha genes a situation that is prefectly compensated.

In my opinion you should take into account the quality of the ultrasound equipment that you are using to detect possible fetal DS markers. It is a complex matter, in addition to how Olena says it influences the experience of the ultrasound operator and the time that can be dedicated to each patient.

judith

@Saad Alaraji

Is it clinically accepted that somatic mutation profile can be used to detect breast cancer?

Can you provide some clinical reports regarding that?

You are welcome Panayiotis. I have been doing this for over 40 years now. Most of what we know was obtained empirically, because no "kits" were available with in depth technical information. I am attaching a paper that was just published. It contains a fair number of techniques that are applicable for all systems, not just ours. If you have any questions, just ask.

Robert is right. In the pharmacokinetics/pharmacodynamics context of drug metabolism, ADME refers to Absorption, Distribution, Metabolism and Excretion/Elimination.

Big numbers beyond say 1 in 10 represent a challenge to many patients but many can relate to days of the year. So if a risk is 1 in 750 you could give as an example - if you pick a date sometime in the next 2 years and I can correctly guess the date, that is about 1 in 700.

For 1 in 18000 you could say if you pick a date sometime in the next 5 years and I can correctly guess the date, that is about 1 in 18000. 

Karen,  I will send it too you today.    Nancy

Thank you Emilija and Abdulkarim

Hi Luis Alberto,

see the attached, it may answer your question .

sorry for the initial mail without the attachment

I gather you mean an NIPT result showing Turner's Syndrome (XO genotype). As NIPT is a screening test, it would be important to consider confirming the diagnosis with a diagnostic test ie chorionic villus sampling or amniocentesis. The obtained sample should be sent for chromosome culture to confirm the diagnosis.

Once confirmed, evaluation of the fetus for associated abnormalities can be performed by ultrasound. Hear defects, in particular, may occur in 15-30% of fetuses. Subsequent management should be individualised. The prognosis for a fetus without structural abnormalities is good. Intellectual development is normal and, with the exception of premature ovarian failure, is not different from a non-affected individual.

Hi Luis

Sorry, I didn't realize that - of course the possibilities are dependent on availability. I was just (too) influenced of many recent discussions with colleagues from Denmark and the Nordic countries, including some who have the technology available, but don't use it.

Bw

Olav

I assume that you already looked at the databasaes (e.g. DESIPHER) and came up empty. Then, get the transmitting father's phenotype. If the father has the same or very similar features there is a reasonable chance that this is causal. In that case, look further in the family for any history suggesting dominant inheritantce. In dominant pedigrees, it does not take too many affected to get a LOD of 3, the definitive proof. 

If no onr in the father'd family is unaffected, it could be irrelevant or a "susceptibility factor" requiring additional genetic or envirnomental input. In that case, you are dealing with a complex trait and you will need anywhere from dozens to thousands (depending on the strength of the effect) of similarly affected probands to prove it. Discouraging, I know, but such are the limitations of human knowledge.

Whenever screening for trisomy is based on cell free fetal DNA (cfDNA), the fetal fraction should be above 10%. If it is less then 4%, the labs won't give a result but if it is between 4 and 10% you will still get a result which, however, is less reliable. A chromosome 21 comprises about 0.75% of the genome, disomy 1.5% and trisomy 21 2.25%, respectively. If the cfDNA concentration is 15% and if there is fetal trisomy 21, then 85% will be of maternal origin and disomic while 15% will be trisomic: 85% x 1,5% + 15% x 2,25% = 1.61% compared to 1.50%. If the fetal fraction is only 5%, then  there will be only 1.54% of chromosome 21 DNA. That clearly indicates why the detection rates goes down. Wright et al. recently demonstrated that the detection rate for trisomy 21 in cases with fetal fractions of 9,8,7,6, 5% and 4% is 100%, 100%, 99,8%, 97,6%, 87,4% and 62,1%. On the webpage of Natera there is a graph indicating that about a fourth of all tests have a cfDNA concentration of less than 10%.

Thats why it is so important to focus on the fetal fraction when reading the report.

Hope this helps,

Best wishes

Oliver 

It would be ideal to use fetal cells circulating in the maternal system. Before Dennis Lo et al. found that there is placental DNA in the maternal system, some studies were made focusing on fetal cells. However, these cells are extremely rare and it is difficult to collect them. In addition they persist for years, so that you will find fetal cells in a current pregnancy that comes from a previous one. In terms of screening for trisomy, the results of these studies (NIFTY) were not that promising, in fact worse that first trimester screening. If however, it is possible to overcome these limitations, fetal cells could be a key towards screening for chromosomal defects and other disorders.

My current opnion is under publication but my recommandation:

Pregnancy care protocol: (not depend on maternal age but all times RR measurement is necessary on the booth upper limb)

Get EHR/FHR on the early pregnancy if low or high there will be a high risk pregnancy.

Get biochemisty to observe maternal blood at 8 weeks. (GP or OBS)

Get the CRL at 10th of pregnancy, and use these date to calculate the real GA.

Do an extended fetal scan between 11-14+6(13+6 if you follow FMF criteria). (here you can follow-up the longbones FL and HL (early IUGR) and BPD+IT (neural defects) and NT+DVPI+facial marker (trisomy). (High risk --> NIPT or invasive procedure)

Do biometry scans every 4-to-6 weeks in the second trimester to find to increasement of the values.

3rd trimester depends on the local infrastructure.

Prevention:

Folates - neural tude and cardiac defects,

B6- againgst pregnancy symptoms

aspirin - preeclapsia

Omega-3 acids: IQ incresement

Combined: O3 and folates can decrease the rate of autism (preliminary results)

Dear Malgorzata, i fully agree with Najmeh ,CNV testing should be done for a pregnant women having risk of fetal abnormalities.if the  tests become available with non invasive way it will help to detect the fetal abnormalities without disturbing the pregnancy.seeing the cost effectiveness and need in the high risk group of preganancies i feel still we should go for women at high risk for fetal abnormalities.

Oxford Gene Technology also has an oligo array, one of the CytoSure chips.

You can find samples of the reports in this article:

Http://onlinelibrary.wiley.com/doi/10.1002/ijc.28809/abstract

its a bit of a jump but high glycolytic activity in the blood of downs patients could be inhibitied by a ketone supplementation which could correct for the metabolic imbalance and up regulate mitochondrial functions including apoptotic pathways and greater developmental control

Patient DNA should be tested for deletion/duplication by MLPA for example. Most importantly what is the status of her partner?

Prenatal diagnosis is certainly possible from invasive fetal testing - CVS/amnio/fetal blood sampling- so the earliest would be from 11 weeks onwards. To date non-invasive diagnosis (ie using free fetal DNA in the maternal circulation) has been more successful for beta Thal than for Sickle although the technique is the same and refinement of the technique may allow better detection that has so far been reported.