简介:Luscan-Lumish综合征(LLS)目前被认为是一种罕见的以过度生长为特征的疾病,大头畸形,肥胖,I型Chiari畸形,和语言迟钝。到目前为止,全球只有少数LLS病例登记,但没有来自中国的报道。为了更深入地了解本病的临床和遗传特点,本研究调查了一个由SETD2基因杂合变异引起的LLS中国男孩。方法:对患者进行临床检查,收集其家族病史。进行基因检测以确定遗传病因。结果:先证者是一名5岁7个月大的男孩,他因“在幼儿园学得很慢”而被转诊到我们医院。与同龄人相比,该孩子有运动和语言发育迟缓的历史。入院后,体格检查显示身高和大头畸形是主要表现,除了智力评估的评分相对较低以及异常的MRI图像外,还显示出略微较短的call体,并伴有轻度较薄的call体。全外显子组测序(WES)揭示了杂合的c.2514_2516delTAG(p。SETD2基因中的Ser838del)变体,随后被鉴定为新的从头变体。根据美国医学遗传学和基因组学学院(ACMG)公布的标准化遗传变异分类,变种,致病性分析结果表明PS2+PM2_支持+PM4被确定为可能致病性。通过文献综述,总结了15例LLS的临床表型,包括8例过度生长(53%),13例(87%),发育迟缓11例(73%),自闭症8例(53%),和7例特殊面部特征(47%)。此外,7例颅脑MRI表现异常。尽管15名患者的突变位点因病例而异,它们在整个SETD2基因中表现出均匀分布的模式,包括5个错义突变,5个移码突变和5个无义突变。结论:LLS,直到最近几年才被认可,被鉴定为由SETD2基因突变引发的常染色体显性综合征。作为LLS在中国的第一份报告,在我们的研究中,该病例被证明与以前从未报道过的独特类型的SETD2基因突变有关,这被认为丰富了SETD2基因的突变谱,加深临床医生对这种疾病的认识。
Introduction: Luscan-Lumish syndrome (LLS) is currently recognized as a rarely-observed condition featured with overgrowth,
macrocephaly, obesity, type I Chiari malformation, and linguistic retardation. So far, there have been only a few LLS cases registered worldwide, but with none of them reported from
China. To acquire a deeper understanding on the clinical and genetic features of this disease, a Chinese boy with LLS caused by a heterozygous variant in SETD2 gene was investigated in the present study. Methods: The patient was clinically examined and the medical history of his family was collected. Genetic testing was performed to determine the genetic etiology. Results: The proband was a boy aged 5-year-7-month-old, who was referred to our hospital due to \"being a slow learner in kindergarten\". The child had a history of delayed motor and language development in comparison to his peers. After admission, physical examination revealed tall stature and
macrocephaly as the major manifestation, in addition to a relatively lower rating in intelligence assessment as well as abnormal MRI images showing a slightly shorter corpus callosum accompanied by a mildly thinner corpus callosum body. Whole exome sequencing (WES) revealed a heterozygous c.2514_2516delTAG (p.Ser838del) variant in SETD2 gene, which was subsequently identified as a novel de novo variant. According to the standardized genetic variant classification published by the American College of Medical Genetics and Genomics (ACMG), the variant, with a pathogenicity analysis result indicating PS2 + PM2_Supporting + PM4, was determined to be likely pathogenic. Through literature review, the clinical phenotypes of the 15 LLS cases were summarized, including 8 cases of overgrowth (53%), 13 cases of
macrocephaly (87%), 11 cases of developmental delay (73%), 8 cases of autism (53%), and 7 cases of special facial features (47%). Besides, abnormal craniocerebral MRI findings were noticed in 7 cases. Despite that the mutation sites of the 15 patients varied from case to case, they showed a uniformly distributed pattern throughout the whole SETD2 gene, including 5 missense mutations, 5 frameshift mutations and 5 non-sense mutations. Conclusion: LLS, not having been recognized till recent years, is identified as an autosomal dominant syndrome triggered by SETD2 gene mutation. As the first report of LLS in
China, the case in our study was proved to be associated with a unique type of SETD2 gene mutation that has never been reported previously, which is believed to enrich the mutation spectrum of SETD2 gene and also, deepening the clinicians\' understanding on the disease.