AbstractBackgroundPseudohypoparathyroidism (PHP) is a series of diseases related to pathological changes and neurocognitive and endocrine abnormalities, mainly due to theGNASmutation on chromosome 20q13.2, which weakens receptor‐mediated hormone signal transduction. Considering its complex genetic and epigenetic characteristics,GNASmay produce complex clinical phenotypes in families or sporadic cases. This study presented a case of familial PHP caused by a deletion mutation in the 20q13.2 region.Methods and ResultsThe proband and her second daughter had PHP, and the proband's mother had pseudo‐PHP. Whole‐genome sequencing revealed that the proband had an 849.81 kb deletion spanningGNASnear the maternal 20q13.2 chromosome. Multiplex ligation‐dependent probe amplification methylation analysis indicated that the proband as well as her mother and second daughter had seemingly abnormalGNASmethylation. This is different from the phenotype (feeding difficulty, slow growth, and special facial features) of previously reported cases with the deletion of fragments near the 20q13.2 chromosome.ConclusionsThis report demonstrated the variability of 20q13.2 deletion phenotypes and the clinical importance of using multiple molecular genetic detection methods.