Caregiver-reported characteristics of children diagnosed with pathogenic variants in KDM5C.
Caregiver-reported characteristics of children diagnosed with pathogenic variants in KDM5C.
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护理人员报告的被诊断患有 KDM5C 致病性变异的儿童的特征。
DOI：
10.1002/ajmg.a.62381
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Shulman LH
中科院分区：
文献类型：
--
作者：
Hatch HAM;O'Neil MH;Marion RW;Secombe J;Shulman LH
赖氨酸脱甲基酶5C（KDM 5C）基因的功能缺失变体约占X连锁智力残疾（ID）病例的0.7%-2.8%，并对患者及其护理人员造成重大负担。迄今为止，在ID患者中报告了45种KDM 5C独特变异。作为一种罕见疾病，其病因和自然史仍然是一个积极研究的领域，治疗仅限于症状管理。先前的研究发现，男性中重度ID患者伴有显著的综合征合并症，如癫痫、身材矮小和颅面畸形。虽然没有很好地表征，但据报道，女性主要表现为轻度至中度ID，其中约一半无症状。在这里，我们提供了37名KDM 5C致病性变异无关个体的所有报告数据，这是迄今为止报告的最大队列。我们发现，高达70%的受影响的女性被报道显示综合征的功能，包括胃肠道功能障碍和听力障碍。此外，超过一半的人报告了自闭症谱系障碍（ASD）的诊断或描述了与该谱系一致的特征。因此，我们的数据提供了进一步的证据，性二态异质性疾病的表现，并表明，致病性变异KDM 5C可能比以前假设的更常见。
Loss of function variants in the lysine demethylase 5C (KDM5C) gene account for approximately 0.7%-2.8% of X-linked intellectual disability (ID) cases and pose significant burdens for patients and their caregivers. To date, 45 unique variants in KDM5C have been reported in individuals with ID. As a rare disorder, its etiology and natural history remain an area of active investigation, with treatment limited to symptom management. Previous studies have found that males present with moderate to severe ID with significant syndromic comorbidities such as epilepsy, short stature, and craniofacial abnormalities. Although not as well characterized, females have been reported to predominantly display mild to moderate ID with approximately half being asymptomatic. Here, we present caregiver-reported data for 37 unrelated individuals with pathogenic variants in KDM5C, the largest cohort reported to-date. We find that up to 70% of affected females were reported to display syndromic features including gastrointestinal dysfunction and hearing impairment. Additionally, more than half of individuals reported a diagnosis of Autism Spectrum Disorder (ASD) or described features consistent with this spectrum. Our data thus provide further evidence of sexually dimorphic heterogeneity in disease presentation and suggest that pathogenic variants in KDM5C may be more common than previously assumed.
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