Study Allan-Herndon-Dudley Syndrome in a Iranian Family with novel SLC16A2 mutation: a case report
Study Allan-Herndon-Dudley Syndrome in a Iranian Family with novel SLC16A2 mutation: a case report
Sareh Bakhshandeh Bavarsad,1Mahya Ebrahimi Nasab,2Seyed Ahmad Mohammadi,3Samira Asadollahi,4Seyed Ali Madani Manshadi,5Seyed Mehdi Kalantar,6,*
1. Department of Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 2. Meybod Genetic Research Center, Yazd, Iran. Yazd Welfare Organisation, Yazd, Iran 3. Meybod Genetic Research Center, Yazd, Iran. Yazd Welfare Organisation, Yazd, Iran 4. Department of Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Research Center for Food Hygiene and Safety, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 5. Meybod Genetic Research Center, Yazd, Iran. Yazd Welfare Organisation, Yazd, Iran 6. Meybod Genetic Research Center, Yazd, Iran
Introduction: A deficiency of monocarboxylate transporter 8 (MCT8), which is encoded by the SLC16A2 gene known as Allan-Herndon-Dudley syndrome (AHDS). Xq13.2 is where the SLC16A2 gene is found. The SLC16A2 gene is in charge of making it easier for thyroid hormone to cross the blood-brain barrier and enter cells, including active T3 and T4. A variety of variants, including missense, nonsense, insertion, deletion, and splicing variants, can result from mutations in the SLC16A2 gene. This neurodevelopmental condition is characterized by thyroid functioning abnormalities as well as delays in mental and motor development. In patients with AHDS, the degree of delayed myelination varies. This variation makes clinical diagnosis difficult and frequently results in underdiagnosis of the condition
Methods: whole-exome sequencing (WES) and data analysis On the patient's pripheral blood sample sample were carried out. The mutation was confirmed by Sanger sequencing in the patient , his mother and his brother
Results: We reported a six-year-old with AHDS diagnosis and pathogenic novel deletion mutation(c.467_469del/p.Phe156del) in the SLC16A2 gene manifesting normal levels T3,T4 and TSH. Additionally, three pathogenic variants have been reported in the proband in the genes TDP2, ALDOB and PMFBP1 as secondry finding. Common symptoms in both Proband and his brother include frequent vomiting in infancy, seizures, developmental delay accompanied by speech difficulties, muscle atrophy and body hypotonia, clenched fists, sclerosis, and skull region depression in the Proband, as well as epilepsy. The MRI result for the Proband has been normal. The mother, who is a carrier of this mutation, had a small right ear and atrophy of the right ear canal was observed. Furthermore, she has experienced two miscarriages in the first and fourth pregnancies.
Conclusion: The study of the familial case afflicted with the Allan-Herndon-Dudley syndrome highlights challenges and complexities associated with diagnosing rare genetic disorders. Through the utilization of next-generation sequencing (NGS) technology, a powerful tool in the field of genetics, a definitive diagnosis was achieved for the affected individuals.We identified a novel mutations in the MCT8 (SLC16A2) gene in two son from a family with AHDS by Next Generation Sequencing. The tests related to the levels of T3,T4, and TSH have been normal, and no specific issue was observed in the MRI of the proband. This confirms the presence of a broad spectrum of symptoms in this disease, which has made the diagnosis itself challenging.