Cohen syndrome, an autosomal recessive syndrome, is a rare syndrome with diverse clinical manifestations including failure to thrive, hypotonia, hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, neutropenia and a friendly character. It is associated with mutations of the vacuolar protein sorting 13 homolog B (VPS13B) gene, which is involved in the development of the ocular, hematological and central nervous systems. This gene encodes a transmembrane protein playing a crucial role in preserving the integrity of the Golgi complex. To date, more than 150 mutations of VPS13B have been reported in over 200 Cohen syndrome patients. Missense or nonsense mutations are the most common mutations. A 4-year-old girl, born to consanguineous parents, was referred to the pediatric clinical immunology outpatient clinic for investigation of recurrent neutropenia with a history of recurrent infections in the past year. On physical examination, she had the characteristic facial features of Cohen syndrome, developmental delay and speech disorder. She had a cheerful disposition, and her mother gave a history of feeding difficulties in her first months of life. She did not present any ophthalmologic or cardiac abnormalities. Her lab results revealed moderate neutropenia. Serum IgG, IgM, IgA and IgE levels were normal. She fulfilled the clinical diagnostic criteria for Cohen syndrome. WES revealed a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49). Currently, she is not experiencing any severe problem, and she undergoes irregular medical treatment once her neutrophil count decreases under the normal limit. Her verbal and motor abilities have improved as a result of speech and occupational therapies. We reported a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49) in a 4-year-old girl with Cohen syndrome. Cohen syndrome should be considered in differential diagnosis of any child with intellectual disability and neutropenia.

中文翻译：

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Cohen综合征中的新型VPS13B突变：病例报告和文献复习。

科恩综合症是一种常染色体隐性遗传综合症，是一种罕见的综合症，具有多种临床表现，包括failure壮失败，肌张力低下，关节活动过度，小头畸形，智力障碍，颅面和四肢异常，中性粒细胞减少和友好的性格。它与液泡蛋白排序13同系物B（VPS13B）基因的突变有关，该基因与眼睛，血液学和中枢神经系统的发育有关。该基因编码跨膜蛋白，在维持高尔基体的完整性方面起着至关重要的作用。迄今为止，已在200多名Cohen综合征患者中报告了150多个VPS13B突变。错义或无意义的突变是最常见的突变。一个四岁的女孩，由近亲的父母生，被转诊至儿科临床免疫学门诊以调查过去一年中有反复感染史的复发性中性粒细胞减少症。经身体检查，她具有Cohen综合征，发育延迟和言语障碍的特征性面部特征。她性格开朗，母亲在出生后的头几个月里曾经历过喂养困难的历史。她没有出现任何眼科或心脏异常。她的实验室检查结果显示出中性粒细胞减少。血清IgG，IgM，IgA和IgE水平正常。她符合Cohen综合征的临床诊断标准。WES在VPS13B（LRG_351t1：c.7095del; p.Ser2366AlafsTer49）中揭示了一种新型的纯合移码变异。目前，她没有遇到任何严重的问题，并且一旦中性粒细胞计数下降到正常范围以下，她将接受不规则的医疗。由于言语和职业疗法，她的言语和运动能力得到了提高。我们在一个4岁的Cohen综合征女孩中报道了VPS13B（LRG_351t1：c.7095del; p.Ser2366AlafsTer49）中的一种新的纯合移码变异。在对任何智障和中性粒细胞减少症儿童进行鉴别诊断时，应考虑科恩综合症。