Helm Benjamin M, Powis Zoe, Prada Carlos E, Casasbuenas-Alarcon Olga L, Balmakund Tonya, Schaefer G B, Kahler Stephen G, Kaylor Julie, Winter Susan, Zarate Yuri A, Schrier Vergano Samantha A
Department of Medical and Molecular Genetics, Indiana University School of Medicine and Riley Hospital for Children at IU Health, Indianapolis, Indiana.
Ambry Genetics, Department of Clinical Genomics, Aliso Viejo, California.
Am J Med Genet A. 2017 Oct;173(10):2814-2820. doi: 10.1002/ajmg.a.38404. Epub 2017 Aug 17.
While X-linked intellectual disability (XLID) syndromes pose a diagnostic challenge for clinicians, an increasing number of recognized disorders and their genetic etiologies are providing answers for patients and their families. The availability of clinical exome sequencing is broadening the ability to identify mutations in genes previously unrecognized as causing XLID. In recent years, the IQSEC2 gene, located at Xp11.22, has emerged as the cause of multiple cases of both nonsyndromic and syndromic XLID. Herein we present a case series of six individuals (five males, one female) with intellectual disability and seizures found to have alterations in IQSEC2. In all cases, the diagnostic odyssey was extensive and expensive, often including invasive testing such as muscle biopsies, before ultimately reaching the diagnosis. We report these cases to demonstrate the exhaustive work-up prior to finding the changes in IQSEC2 gene, recommend that this gene be considered earlier in the diagnostic evaluation of individuals with global developmental delay, microcephaly, and severe, intractable epilepsy, and support the use of intellectual disability panels including IQSEC2 in the first-line evaluation of these patients.
虽然X连锁智力障碍（XLID）综合征给临床医生带来了诊断挑战，但越来越多已被认可的疾病及其遗传病因正在为患者及其家庭提供答案。临床外显子组测序技术的应用正在拓宽识别先前未被认为会导致XLID的基因突变的能力。近年来，位于Xp11.22的IQSEC2基因已成为多例非综合征型和综合征型XLID的病因。在此，我们报告了一个包含六名个体（五名男性，一名女性）的病例系列，这些个体均有智力障碍和癫痫发作，且被发现IQSEC2基因存在改变。在所有病例中，诊断过程漫长且费用高昂，往往包括肌肉活检等侵入性检查，最终才得以确诊。我们报告这些病例是为了展示在发现IQSEC2基因改变之前所进行的详尽检查，建议在对全球发育迟缓、小头畸形和严重难治性癫痫患者进行诊断评估时应更早考虑该基因，并支持在对这些患者进行一线评估时使用包含IQSEC2的智力障碍检测组合。
