Novel SLC16A2 mutations in Chinese patients with Allan-Herndon-Dudley Syndrome

Abstract

We aimed to delineate the clinical profiles of Chinese patients with Allan-Herndon-Dudley Syndrome (AHDS), an X-linked intellectual disability caused by SLC16A2 mutation and affecting males only. Clinical features of five males from four Chinese families, who manifested with severe cognition impairment, developmental delay, hypotonia accompanied by dystonia, were described and summarized. All of them displayed a distinctive thyroid hormone change, with increased FT3, reduced FT4, and normal TSH. Three of them had neuroimaging tests and all presented with hypomyelination. Two of them demonstrated some facial anomalies, including long face, narrow forehead and tent mouth. Targeted next-generation sequencing associated with intellectual disability was performed. Four SLC16A2 mutations (c.916C>T, p.Gln306*; c.61G>T, p.Glu21*; c.695 699delATGGT, p.Asn232Sfs*7; c.42delC, p.Trp15Glyfs*69) were identified, of which three SLC16A2 mutations were novel. Our findings expand mutational spectrumof SLC16A2 and provide support for delineating the clinical features of Chinese patients with AHDS. In addition, this is the first report of AHDS in Chinese cohort. We recommend that male patients with intellectual disability, developmental delay and severe hypotonia, especially those with distinctive thyroid hormone change should be tested for SLC16A2 mutations.