Novel SLC16A2 Frameshift Mutation as a Cause of Allan-Herndon-Dudley Syndrome and its Implications for Carrier Screening

Peng Lin,1,2,* Huituan Liu,3,* Jiwu Lou,1,2 Guizhen Lyu,4,5 Yanwei Li,4 Peiqing He,1,2 Youqing Fu,1,2 Ronghua Zhang,1,2 Yuqiong Zhang,3 Tizhen Yan1,2 1Prenatal Diagnostic Centre, Dongguan Maternal and Children Health Hospital, Dongguan, Guangdong, People’s Republic of China; 2Dongguan Key Laboratory of Precision Medicine for Prenatal Diagnosis of Genetic Diseases, Dongguan, Guangdong, People’s Republic of China; 3Department of Children’s Rehabilitation, Dongguan Maternal and Children Health Hospital, Dongguan, Guangdong, People’s Republic of China; 4Dongguan Key Laboratory of Clinical Medical Test Diagnostic Technology for Oncology, Dongguan Labway Medical Testing Laboratory Co., Ltd., Dongguan, Guangdong, People’s Republic of China; 5Dongguan Molecular Diagnostic Technology and Infectious Disease Medical Test Engineering Research Centre, Dongguan Labway Medical Testing Laboratory Co., Ltd., Dongguan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tizhen Yan, Email [email protected] Yuqiong Zhang, Email [email protected]: Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked neurodevelopmental disorder caused by mutations in the solute carrier family 16-member 2 (SLC16A2) gene. This syndrome leads to significant psychomotor disabilities, thyroid dysfunction, and abnormal brain development. This case report describes the genetic cause of AHDS in a male proband and to expanding the mutation spectrum of the SLC16A2 gene.Methods: A blood specimen was collected from a one-year-old child with delayed development and abnormal thyroid function and this was followed by whole-exome sequencing (WES) was performed on the proband to identify potential genetic mutations. Sanger sequencing was subsequently used to confirm the findings and determine the inheritance pattern of the mutation within the family.Results: The proband, who presented with developmental delay, thyroid dysfunction, and abnormal brain development, was found to have a novel hemizygous frameshift mutation, c.513_538del (p.Ile172Cysfs*60), in the SLC16A2 gene (NM_006517.5). This mutation was inherited from his asymptomatic mother, confirming the X-linked inheritance pattern. The mutation is classified as likely pathogenic, contributing to the clinical presentation observed in the proband.Conclusion: This study identified a novel frameshift mutation in the SLC16A2 gene associated with AHDS, thereby expanding the known mutation spectrum of this gene. Given the significant impact of AHDS on neural development and hormone secretion, it is recommended that this gene be included in carrier screening panels in China, particularly for families with a history of related neurodevelopmental disorders.Keywords: SLC16A2 gene, Allan-Herndon-Dudley syndrome, thyroid pathology, neurotransmitter development