Parents of a 4 year old child were referred for genetic study.

The child had “jaundice” with fluid in his tummy for over a year and died because of the same.

Parents are planning second pregnancy and are worried that the second pregnancy might also be affected as they were told that their first child could have died because of some “inherited” disease.

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How come their child has “inherited disease when they are healthy?

What could have gone “wrong” ? What tests will guarantee that their next

child will be healthy? How and where the tests will be done?

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Patterns of inheritance will easily explain this...

But there are spontaneous mutations and there is a role of environmental factors also, e.g. tobacco

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Malfunctioning of a gene/s

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It is a functional area on a chromosome which is made up of various nucleotides, which will manufacture various proteins, that will carry out various bodily functions.

If it works well, our body works well If it is not working well, a genetic defect, then

our body may have some malfunction.

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Gene

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A car engine has several parts If one part is defective,

the engine may not work, works defectively or it may breakdown half way through

Same thing will happen, when a gene has some defective parts

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Chromosomal abnormalities or mutation or aberration are according to their structural and numerical changes they termed as

Structural abnormalities Numerical abnormalities

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Gene mutations have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. The types of mutations include:

Missense mutation Nonsense mutation Insertion Deletion Duplication Repeat expansion

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Normal function Partially normal function Totally non-functional

Lethal Compatible with life in a limited or compromised

way

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One which is frequently seen in a given disease due to genetic defect

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If a Bajaj scooter is not working, most commonly you have to tilt it !!

But there could be other reasons also, the uncommon causes 15

Indians may have different mutations responsible for Wilson’s disease than Caucasians

Bajaj scooter and Honda may not start for entirely different reasons

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More mutations we test, more chances are that we will be more confident in your predictions

So we have to know mutations in our population, otherwise we may keep making mistakes.

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We can’t proceed further without knowing what was the disease and what was the mutation responsible for their first child’s, “the proband’s”, death

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All we can offer them is the common mutation tests for commonly occurring genetically inherited liver diseases.

As we may understand, this may lead to lots of problems.

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On the other hand.... Had we known the disease and the mutation

in the proband, then certainly we can test the fetus for that particular mutation and reasonably certainly counsel the parents.

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If we don’t know what happened to the proband, we can’t do much in the next pregnancy

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Carrier testing before conception Best example is screening for DMD

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Testing the fertilized embryo for genetic dosing.

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By amniotic fluid at 16 weeks; and Chorion Villous Biopsy at 12 weeks Triple marker test

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By New Born Screening (NBS)

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Some disorders that "run in families" can be traced to shared environmental exposures rather than any inherited susceptibility. In addition, some mutations detected by a positive test may never lead to disease.

Furthermore, because existing tests look only for the more common mutations in a gene, but some disease-causing mutations may escape detection.

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Gene can go wrong in various ways. This is called mutation.

Different races have different mutations, some common and some uncommon and what applies in Caucasians may not apply in India.

Looking for mutation in sibling without knowing mutation in the proband is no..no..

But a reliably diagnosed mutation could be the most accurate way of diagnosing a genetic diseases.

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