García-de Teresa Benilde, González-Del Angel Ariadna, Reyna-Fabián Miriam Erandi, Ruiz-Reyes María de la Luz, Calzada-León Raúl, Pérez-Enríquez Bernardo, Alcántara-Ortigoza Miguel Angel
1 Laboratorio de Biología Molecular, Departamento de Genética, Instituto Nacional de Pediatría , Mexico City, Mexico.
Thyroid. 2015 Mar;25(3):361-7. doi: 10.1089/thy.2014.0284. Epub 2015 Feb 6.
Allan-Herndon-Dudley syndrome (AHDS) is an X-linked type of mental retardation resulting from hindered thyroid hormone access to neurons. Clustered nonrecurrent deletions of SLC16A2 exon 1 have been described in three patients with AHDS. We report a fourth patient with such a deletion and discuss possible mechanisms leading to these rearrangements.
A three-and-a-half-year-old male with clinical and biochemical AHDS phenotype and a history of normal neonatal screening for hypothyroidism underwent SLC16A2 molecular analysis. Unexpectedly, he showed skeletal signs of hypothyroidism.
The exons of the SLC16A2 (MCT8) gene and the sequences surrounding exon 1 were amplified using PCR. The patient had a 36-kb deletion affecting exon 1 of SLC16A2. The deletion junction was subjected to bioinformatic analyses, along with two other reported exon 1 deletion junctions, identifying possible sequence features and mechanisms responsible for such genomic rearrangements.
DISCUSSION/CONCLUSION: This patient had a classic AHDS phenotype with an unexpectedly large anterior fontanel and delayed bone age and dentition. Bioinformatic analyses suggested that exon 1 deletions in patients with AHDS are caused by microhomology-mediated replicative-based and nonhomologous end-joining mechanisms. Rearrangement susceptibility may be due to the size of intron 1 and the percentage of repeat sequences.
艾伦 - 赫恩登 - 达德利综合征（AHDS）是一种X连锁型智力障碍，由甲状腺激素进入神经元受阻所致。在三名AHDS患者中描述了SLC16A2外显子1的成簇非复发性缺失。我们报告了第四例有这种缺失的患者，并讨论了导致这些重排的可能机制。
一名3岁半男性，具有临床和生化AHDS表型，新生儿甲状腺功能减退筛查结果正常，接受了SLC16A2分子分析。出乎意料的是，他出现了甲状腺功能减退的骨骼体征。
使用PCR扩增SLC16A2（MCT8）基因的外显子和外显子1周围的序列。该患者有一个36kb的缺失，影响SLC16A2的外显子1。对缺失连接点进行了生物信息学分析，连同另外两个报告的外显子1缺失连接点一起，确定了可能导致这种基因组重排的序列特征和机制。
讨论/结论：该患者具有典型的AHDS表型，前囟门意外地大，骨龄和出牙延迟。生物信息学分析表明，AHDS患者的外显子1缺失是由微同源性介导的基于复制和非同源末端连接机制引起的。重排易感性可能归因于内含子1的大小和重复序列的百分比。
