Willis Erin, Moore Steven A, Cox Mary O, Stefans Vikki, Aravindhan Akilandeswari, Gokden Murat, Veerapandiyan Aravindhan
Division of Neurology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Pathology, University of Iowa Carver College of Medicine and Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Iowa City, IA, USA.
Child Neurol Open. 2022 Apr 28;9:2329048X221097518. doi: 10.1177/2329048X221097518. eCollection 2022 Jan-Dec.
Limb-girdle muscular dystrophy R9 (LGMD2I, LGMDR9) is an autosomal recessive disorder caused by pathogenic variants in the fukutin-related protein () gene. We describe a 17 year old boy with LGMDR9 whose symptoms began at age 5 years. Muscle histopathology, immunostaining, and western blotting were consistent with a dystroglycanopathy. Genetic testing identified maternal inheritance of the most common pathogenic variant c.826C>A (p.L276I). Also detected was a novel insertion and duplication on the paternally inherited allele: a single nucleotide insertion (c.948_949insC) and an eighteen nucleotide duplication (c.999_1017dup18) predicted to result in premature translation termination (p.E389*). Based on the clinical features and course of the patient, heterozygosity for the common pathogenic variant, and abnormal glycosylation of alpha-dystroglycan, we suggest that the novel insertion and duplication are pathogenic. This case expands the genetic heterogeneity of LGMDR9 and emphasize the importance of muscle biopsy for precise diagnosis.
肢带型肌营养不良症R9（LGMD2I，LGMDR9）是一种常染色体隐性疾病，由福金相关蛋白（）基因的致病性变异引起。我们描述了一名患有LGMDR9的17岁男孩，其症状始于5岁。肌肉组织病理学、免疫染色和蛋白质印迹与糖基化肌营养不良蛋白病一致。基因检测确定了最常见致病性变异c.826C>A（p.L276I）的母系遗传。在父系遗传的等位基因上还检测到一个新的插入和重复：一个单核苷酸插入（c.948_949insC）和一个18个核苷酸的重复（c.999_1017dup18），预计会导致翻译提前终止（p.E389*）。基于患者的临床特征和病程、常见致病性变异的杂合性以及α-糖基化肌营养不良蛋白的异常糖基化，我们认为新的插入和重复具有致病性。该病例扩展了LGMDR9的遗传异质性，并强调了肌肉活检对于精确诊断的重要性。
