Biallelic human ITCH variants causing a multisystem disease with dysmorphic features: A second report
Biallelic human ITCH variants causing a multisystem disease with dysmorphic features: A second report
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DOI：
10.1002/ajmg.a.61169
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发表时间：
2019-07-01
影响因子：
2
通讯作者：
Wilson, Louise C.
中科院分区：
文献类型：
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作者：
Brittain, Helen K.;Feary, Johanna;Wilson, Louise C.
我们报告了一名23岁女性，其瘙痒基因（瘙痒E3泛素蛋白连接酶，小鼠OMIM60649同源基因）双等位基因截断变异与明显的身材矮小、严重的早期慢性肺病（如哮喘）、畸形的面部特征和手指对称的camptodyly，但智力正常。这种情况以前只报道过一次（Lohr等人，American Journal of Human Genetics, 2010, 86, 447-453），在一个旧序阿米什家族的10名儿童中发现了一种纯合子移码截断变异体，这种变异体与发育不良、慢性肺病、运动和认知延迟以及包括自身免疫性肝炎、肠病、甲状腺功能减退和糖尿病在内的各种自身免疫性疾病有关。这种情况在OMIM中被列为自身免疫性疾病，多系统面部畸形（OMIM613385）。患者的临床过程以及面部和肢体的畸形特征与患者有密切的重叠。我们认为，明显的综合征性身材矮小、慢性肺部疾病和畸形（伴有或不伴有认知障碍和更广泛的自身免疫性疾病）是独特的。
We report a 23 year old female with biallelic truncating variants in the ITCH (Itchy E3 Ubiquitin protein ligase, mouse homolog of; OMIM60649) gene associated with marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. The condition has only been reported once previously (Lohr et al., American Journal of Human Genetics, 2010, 86, 447-453) in 10 children from an Old Order Amish family found to have a homozygous frameshift truncating variant in association with failure to thrive, chronic lung disease, motor and cognitive delay, and variable autoimmune diseases including autoimmune hepatitis, enteropathy, hypothyroidism, and diabetes. The condition is listed in OMIM as Autoimmune disease, Multisystem with Facial Dysmorphism (OMIM613385). The clinical course as well as the dysmorphic facial and limb features overlap closely with our patient. We believe the triad of marked syndromic short stature, chronic lung disease, and dysmorphism (with or without cognitive impairment and wider autoimmune involvement) is distinctive.