Table 6 Examples of Mendelian diseases
Inheritance patternDiseaseGene/regionNature of variantsEstimated frequency
Autosomal dominantGlut1 deficiency (De Vivo disease)SLC2A1Mutations reduce or eliminate functionRare, approximately 1/90000
Osteogenesis imperfecta (brittle bone disease)COL1A1 or COL1A2 (90%) (also CRTAP or P3H1)COL1A1/COL1A2 – usually missense mutations that lead to protein (collagen) of altered structure6–7/100000
AchondroplasiaFGFR3Activating point mutations1/15000 to 1/40000
Autosomal recessivePhenylketonuriaPAHMany different mutations, including missense, non-sense, splicing mutations1/10000 to 1/15000
Cystic fibrosisCFTROver 2000 different variants known1/2500 to 1/3500 in Caucasians, less common in other ethnic groups
Sickle-cell anaemiaHBBVarious missense variants, gene deletions1/70000 to 1/80000 in the U.S.A., more common in other countries
X-linked recessiveHaemophilia AF8Missense and nonsense mutations1/4000 to 1/5000 males
Duchenne muscular dystrophyDMDUsually deletions or duplications1/3500 to 1/5000 (Duchenne and Becker muscular dystrophy together)
X-linked dominantFragile X syndromeFMR1CGG trinucleotide repeat expansion1/4000 (males), 1/8000 (females)
Rett syndromeMECP2Missense mutations, abnormal epigenetic regulation1/8500 females
X-linked hypophosphatemic ricketsPHEXDeletions, insertions, missense, nonsense, splicing mutations1/20000
Y-linkedNonobstructive spermatogenic failureUSP9YMost commonly deletions1/2000 to 1/3000
  • Diseases are shown together with their inheritance patterns, the affected gene, the most commonly found types of mutation, and estimated incidence rates. Note, some diseases, for example osteogenesis imperfecta (of which there are several forms), can be caused by pathogenic variants in one of a number of different genes.