Monogenic diseases


A genetic disease is caused by a DNA alteration; they are divided in chromosomal disease when there is a numerical or structural chromosomal anomaly (Down syndrome, Turner syndrome, etc..); monogenic diseases if it is present an alteration in a single gene (cystic fibrosis, fragile-X syndrome) or multifactorial polygenic diseas due to the interaction of more altered genes with ambient factors (cardiovascular diseases, diabetes, etc..).

What's a gene?

A gene, is a DNA segment (deoxyribonucleic acid) considered how a word that can have a different meaning depending on the succession of letters (sequence) composing it.
The letters of this special alphabet are chemical compounds called bases and they are only four (A, C, G, T respectively for Adenine, Cytosine, Guanine, Thymine); the words (genes), written in the DNA, the molecule of the life, are very longs (generally thousands of bases) and numerous, about 25.000. The set of genes represents the genetic asset of an individual (genotype). A gene contains the instructions (genetic code) for producing a protein. Each gene encodes for a particular protein, so there are a lot of proteins, eachone with a specific function (ex. the keratin protein forms hair and nails, the trypsin is involved in the food digestion, the dystrophin is present with other protein in muscles). In each individual, all of genes are present in double copy, one on a maternal chromosome and the other on paternal chromosome. Generally the two copies are functiona, that is contain the correct instructions for producing the protein (Fig.1). Exception is represented from individual of male sex which have genes located on the X chromosome in a single copy (hemizygotes).

Ogni gene è presente in doppia copia

Fig.1 – All genes are in double copy, one on the paternal chromosome and the other on maternal one.
A gene contains information as bases sequence (AGTGCT…) for a protein synthesis.

What does it happens when a gene not functions?

In the human population, some individuals have one or two gene copies, with a variation (mutation) in the sequence of the letters, causing the incorrect production of the protein, that is faulty and does not properly its function; this is a case of a genetic diseases. The different gene forms are named alleles, so an allele is normal or changed if respectively the gene is normal or it has an alterations in the sequence of the bases (Fig.2).

Versione (allele) normale e mutata di un gene 
Fig.2 – Normal and mutated version of a gene (allele). Mutated allele encodes for an abnormal protein.
Homozygotes and heterozygous

In the population, individuals with equal alleles for a gene are defined homozygotes; the homozygotes can be normals (wild type) or mutated if either alleles are normal or mutated, with the same mutation in all of the two alleles (Fig.3). Individuals with two different alleles for a specific gene, one normal and one mutated, are defined heterozygous (Fig.3). An individual compound heterozygote have both mutated alleles with two different mutations (Fig.3).

Omozigoti ed eterozigoti 
Fig.3 - Homozygotes and heterozygous
How are classified the monogenic diseases ?

The monogenic diseases are classified for:
1) the chromosomal localization of gene in:
- autosomal disease if a gene is located on autosomes;
- sex-linked (X-linked or Y-linked) If a gene is on a sex chromosomes (X or Y);
2) the effect of the altered gene in:
- dominant if the pathological condition occurs when it is altered only one of the two
copies of the gene
- recessive if the pathological condition occurs only when both gene copies are altered

Could a monogenic genetic diseases be transmitted?

The hereditary transmission (to the successive generation), of the
monogenic disease take place in different ways:
- recessive autosomal pattern
- dominant autosomal pattern
- sex-linked pattern

Genetic counseling

It's a process giving to the patients and their family at risk to disease development, to inform, in a clear terms about the hereditary transmission and its risk in a family, diagnostic options and pre –postnatal treatment.