Monogenic disorders are caused by the inheritance of single gene mutations; alternatively, a monogenic disorder arises as a consequence of a de novo mutation in either the paternal or maternal germ line. The exponential increase in our understanding of the human genome has resulted in the localisation and cloning of a vast number of disease genes which has enabled the precise characterization of the underlying molecular defect in many of these disorders. Single nucleotide substitutions and microdeletions are the major types of disease-related mutations, but more complex mutations have also been described.