Novel frameshift mutation in SLC۱۲A۲ gene associated with severe phenotype of Allan-Herndon-Dudley syndrome (AHDS)

Backgrounds: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked syndrome withneuromuscular involvement characterized by infantile hypotonia, muscular hypoplasia, spasticparaparesis, and cognitive deficiency. It is mostly caused by SLC۱۶A۲ gene (Xq۱۳.۲) mutationswhich encode a transporter protein. Monocarboxylate transporter ۸ (MCT۸) transports thyroidhormone T۳ to nerve. In this study we report a two-and-a-half-year-old boy with AHDSdiagnosis and a novel mutation in SLC۱۶A۲ gene manifesting normal level of T۴ but high levelof TSH hormone.Materials and Methods: We present a two-and-a-half-year-old boy who was admitted to ourclinic for ID evaluation. He was born from unrelated parents. By the time he was ۲۴ days old anincrease was observed in SGOT and SGPT levels which can be a sign of brain damage.Sensorineural hearing loss in the right ear (moderate) and left ear (mild) was detected. He wasunable to walk, speak and feed independently. Blood sample was collected and whole exomesequencing (WES) using Illumina HiSeq۴۰۰۰ platform was performed.Results: A rare c.۱۰۱۵dupT (p. P۳۳۸fs) mutation in SLC۱۶A۲ gene which is hemizygous wasdetected in WES analysis. We consider this mutation as pathogenic mutation which caused thepatient’s phenotype. Heterozygous c.۳۴۴T>A (p. Val ۱۵ Glu) mutation on UFSP۲ gene andheterozygous c.۱۲۳۹۴delC (p. L۴۱۳۲fs) mutation on USH۲A gene are reported as incidentalfindings, these variants were previously reported as pathogenic.Conclusion: In this case, WES as a powerful diagnostic tool helped us to confirm the clinicaldiagnosis of Allan-Herndon-Dudley syndrome. PND (prenatal diagnosis) for future pregnanciesand genetic counseling for other members of family were suggested.

کلیدواژه ها:

Allan–Herndon–Dudley syndrome ، Paroxysmal dyskinesias ، Free triiodothyronine ، SLC۱۶A۲ gene ، Mutation