HOW MANY MENDELIAN DISEASES ARE THERE?
As of July 2014, approximately 7,300 Mendelian diseases have been described. For 3,963 of these, the gene that is mutated and likely responsible for the disease is known (examples are shown in Table 1). It is probable that many more Mendelian diseases will be “solved” as genomic analysis becomes more integrated into clinical practice. For many genes, different genetic variants can have distinct effects on the encoded protein, leading to distinct disease characteristics. For example, different variants may have different effects on the amount of the encoded protein or the activity of the encoded protein. Indeed, the 3,963 unique diseases that have been solved affect only 2,776 genes because different mutations in the same gene can cause different (but often related) disease characteristics.
It is probable that many more Mendelian diseases have yet to be described. There are approximately 20,000 protein-coding genes in the human genome, and variants in many of these genes would be expected to cause human disease. In addition, variants in many of the genes that encode RNAs but do not encode proteins may also lead to disease; however, these have not been studied in detail and the number of known cases is presently limited. It is likely that many more will be found. Of course, some genetic variants may be so deleterious that they result in fetal death and, therefore, will not be observed among the living population.
Table 1. Examples of Genes Implicated in Mendelian Diseases
|APP, PSEN1, PSEN2||Early onset Alzheimer’s disease (AD)||Medications for symptomatic AD: cholinesterase inhibitors, memantine|
|BRCA1, BRCA2||Breast cancer; ovarian cancer||For individuals with disease variants but no disease: frequent monitoring for evidence of cancer; in certain cases preventive surgery (mastectomy and/or removal of the ovaries and fallopian tubes) may be considered|
|CFTR||Cystic fibrosis (CF)||Multiple treatments for symptomatic CF: for example, airway clearance techniques, DNase, ivacaftor for specific CFTR mutations|
|HFE||Hemochromatosis (excessive iron absorption)||For individuals with symptoms: phlebotomy, chelation, diet modification|
|Typical treatment for conditions of aging such as hypercholesterolemia, cataracts, diabetes|