First female with Allan-Herndon-Dudley syndrome and partial deletion of X-inactivation center

Allan-Herndon-Dudley is an X-linked recessive syndrome caused by pathogenic variants in the SLC16A2 gene. Clinical manifestations are a consequence of impaired thyroid metabolism and aberrant transport of thyroid hormones to the brain. Carrier females are generally asymptomatic and may show subtle symptoms of the disease. We describe a female with a complete Allan-Herndon-Dudley phenotype, carrying a de novo 543-kb deletion of the X chromosome. The deletion encompasses exon 1 of the SLC16A2 gene and JPX and FTX genes; it is known that the latter two genes participate in the X-inactivation process upregulating XIST gene expression. Subsequent studies in the patient demonstrated the preferential expression of the X chromosome with the JPX and FTX deletion.

Automated summary

Allan-Herndon-Dudley syndrome is an X-linked recessive disorder caused by pathogenic variants in the SLC16A2 gene, resulting in impaired thyroid metabolism and abnormal transport of thyroid hormones to the brain. A female patient with a complete phenotype of Allan-Herndon-Dudley was found to have a de novo 543-kb deletion on the X chromosome that includes the SLC16A2 gene and JPX and FTX genes, known to play a role in X chromosome inactivation. Studies showed preferential expression of the X chromosome with the deletion of JPX and FTX in the patient.