Duplication of 17q11.2 and Features of Albright Hereditary Osteodystrophy Secondary to Methylation Defects within the GNAS Cluster : Coincidence or Causal?

الملخص EN

We report a case of Albright hereditary osteodystrophy (AHO) in a three-year-old girl with a microduplication at 17q11.2.

The child developed obesity within the first 6 months of life.

A diagnosis of Albright was made at age 2 years when biochemical evidence of parathyroid resistance was found.

No mutations were identified in guanine nucleotide-binding protein G (s) subunit alpha (GNAS1).

Subsequent investigations revealed methylation disturbance at GNAS1A, neuroendocrine secretory protein antisense (NESPAS) and neuroendocrine secretory protein 55 (NESP55) confirming a diagnosis of pseudohypothyroidism type 1B.

A deletion of NESP55 and uniparental disomy chromosome 20 were excluded which suggested that the features of AHO arose through a purely epigenetic mechanism.

Further investigation revealed a de novo microduplication at 17q11.2 encompassing the neurofibromatosis type 1 (NF1) gene.

The combination of two rare de novo events in the same child raises the possibility that duplication of a gene within the 17q11.2 region may have triggered abnormal methylation in the GNAS cluster region on chromosome 20.