ALPL and bone disorder: Some candidate gene studies exploring genetic causes of AFF have investigated, eg, genetic variants in one or more candidate genes such as ALPL, COL1A1, COL1A2, and SOX9 in a small number of patients (<20), identifying only two likely pathogenic variants in COL1A2 and ALPL, respectively.(16, 17, 18) Many other genes associated with monogenic bone disorders have not been investigated for the presence of variants in AFF cohorts.