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Lowe syndrome

Monday, February 9, 2015

What is a mutation?

Mutations call stable changes in the DNA strand that are capable of being inherited.

The truly transcendent mutations to offspring are those present or occur in germ cells (eggs and sperm).

Mutations can lead to small changes, large changes (causing disease: pathogenic mutations) or be silent.

A mutation that we inherited from our parents is called inherited mutation, which occurs in the individual without a parent with the same mutation, it is called de novo mutation.

The Genetic Code

The genetic information is contained in a code consisting of the four nucleotides (adenine, guanine, thymine and cytosine) forming codons (sets of three bases).

Different combinations of three nucleotides (codon) determining a particular amino acid in protein formation (eg UCG combination determines the corresponding amino acid is a serine) or a symbol (starting or stopping of the protein sequence, UAG determined such that the reading is finished gene), as are chains of amino acids porteinas.

The DNA sequence is expressed as a nucleotide sequence, which is expressed as initial:

  • Adenine (A)
  • Cytosine (C)
  • Guanine (G)

Thymidine (T) (in the case of DNA) or uracil (U) (in the case of RNA).

The genetic code is the "reading frame", the sequence of these nucleotides of DNA that determines the amino acid sequence of a protein, just as the letters of the alphabet arranged in a certain order form words and phrases.

Types of mutations

Mutations can occur at three different levels:

  • Molecular (gene or specific): These are mutations at the molecular level and affect the chemical composition of genes, ie the bases or "letters" of DNA.
  • Chromosome: The change affects a chromosome segment (larger than a gene), therefore its structure. These mutations can occur because large fragments (deletion) are lost, duplicated, change places within the chromosome.
  • Genomic: It affects the whole genome, increasing the number of chromosome sets (polyploidy) or reducing it to a single series (haploid or monoploidía) or affect the number of chromosomes individually (by default or by excess), such as trisomy 21 or Syndrome Down.

In the case of Lowe syndrome, mutations are studied in this group of molecular type, both inherited and de novo. Let's see then some of its features:

Molecular or point mutations

A point mutation is a single nucleotide change or a small number of nucleotides. You could compare it with the fact of changing a single letter in a complete sentence.

The DNA sequence of a gene can be altered in different ways. These mutations have different effects on the health of people, depending on where they occur and whether or not alter the essential function of the protein or the normal processes of reading, transcription and protein translation.

Very often in the literature, is respected or preserved in English nomenclature of the types of mutations, as sometimes literal translations lead to confusion. Try to place simultaneously both denominations, to become familiar with both.

We can classify the different types of mutations:

1. Silent mutations:

In this type of mutation is a change in one of the DNA bases so that the nucleotide triplet modified, but still coding for the same amino acid. This is because the genetic code has certain safety margin for each amino acid and various combinations of triplets that determine it.

For example, the triplet CCC CCA determined and that in this position a proline protein is placed. Thus, if this error occurs instead be a silent change, because the amino acid encoded by both triplets is the same, proline.


I am sea salt -> I'm sun sea (meaning varies but do not just lose consciousness)
The cat ate the rat -> The cat ate the hat

2. Missense mutation

This type of mutation is a change in one of the bases of DNA so that the triplet codes for a different amino acid than it should, that is, in that position of the protein will have an incorrect amino acid, which can alter roughly protein function depending on its location and extent.

Example very prematurely truncated:

I am sea salt -> I am salt
The cat ate the rat -> The cat

Example of insertion of 3 bases:

I am sea salt -> Soy EV sea salt
The cat ate the rat -> The trh cat ate the rat

3. Deletion

In this type of mutation are lost one or more bases, i.e., a piece of DNA is lost by altering the protein chain which should be formed and function. This way you can alter the reading frame (see item 8) to form the protein or delete amino acids that are unique to the protein chain. Sometimes deletions are so long that can compromise an entire gene or several contiguous genes.

Example duplication of a number of multiple nucleotide 3 (no change in reading frame):

I am sea salt -> I am salt sea salt sea salt
The cat ate the rat -> The cat ate cat ate cat ate the rat

4. Change reading frame (Frameshift mutation)

This type of mutation is when insertion or loss of base pair reading frame is changed. For decoding, the bases are read in threes, ie each amino acid determine three bases.

If the reading frame is changed, changed the way of grouping these three bases and amino acids are placed wrong having the possibility of a premature STOP triplet. Insertions, duplications and deletions can lead to this type of mutations.

5. Expansion per replicate

Are often not considered mutations puntuales.Se triplet repeats is cuatripletes nucleotide or small DNA sequences 3 or 4 bp repeat in series.

A mutation is a mutation expansion in the number of repetitions has increased, which can make the final protein malfunction.

Paradigmatic diseases such mutations are Fragile X Syndrome or Spinocerebellar ataxias (SCA). In the latter case the nucleotide triplet CAG so that a chain determines glutamines (polyglutamine) repeat

6. Other

Finally there are many types of mutations that do not affect the protein itself, if not to the amount of protein produced and under what circumstances or locations (tissues and cells) occurs. Are due to alterations in the expression of DNA.

Some regions of the DNA have a primary function of regulating the expression of genes are regulatory regions controlling or determining which areas of DNA are silent or are being expressed. Mutations in these regulatory genes can lead to alterations of more than one gene by acting as "conductors".


I am sea salt -> Sos ald elm ar
The cat ate the rat -> Thc tet binds her at

The study sample Lowe syndrome patients has allowed us to know that mutations all patients manifest are different, in a percentage of 95% and of different types.

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