目的:分析1例因SBDS基因复合杂合变异导致的Shwachman-Diamond综合征(SDS)患者的临床特征和遗传特征。
方法:选择2022年2月郑州大学附属儿童医院收治的一名患有SDS的女患儿作为研究对象。收集患儿的临床资料。收集孩子及其姐姐和父母的外周血样本,并进行全外显子组测序(WES)。通过Sanger测序验证候选变体。
结果:孩子,一个1岁1个月大的女孩,主要表现为腹泻,便血,生长迟缓和营养不良,同时转氨酶增加,中性粒细胞和血红蛋白减少。左手腕前后X线显示骨龄明显延迟。结肠镜检查显示,她的结肠直肠粘膜糜烂,肠腔上附着有油性食物残渣。基因测试表明,她拥有SBDS基因的c.258+2T>C和c.100A>G复合杂合变体。c.258+2T>C变异来自她的父亲,已知具有致病性,而另一个来自她的母亲。根据美国医学遗传学和基因组学学院的指南,c.100A>G变异被分类为可能致病(PM1+PM2_支持+PM3+PM5+PP3)。
结论:c.258+2T>C和c.100A>G的复合杂合变体可能在这个孩子的SDS下面。对于儿童难治性腹泻,肝损伤和生长迟缓,SDS应该被怀疑,基因检测可以促进诊断和治疗。
OBJECTIVE: To analyze the clinical features and genetic characteristics of a patient with Shwachman-Diamond syndrome (SDS) due to compound heterozygous variants of SBDS gene.
METHODS: A female child with SDS who was admitted to the Children\'s Hospital Affiliated to Zhengzhou University in February 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her elder sister and parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.
RESULTS: The child, a 1-year-and-1-month-old girl, had mainly manifested with diarrhea, hematochezia, growth retardation and malnutrition, along with increased transaminases and decreased neutrophils and hemoglobin. Anteroposterior X-ray of her left wrist indicated significantly delayed bone age. Colonoscopy revealed that her colorectal mucosa was erosive with oily food residues attached to the intestinal lumen. Genetic testing revealed that she has harbored c.258+2T>C and c.100A>G compound heterozygous variants of the SBDS gene. The c.258+2T>C variant has derived from her father and known to be pathogenic, whilst the other has derived from her mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.100A>G variant was classified as likely pathogenic (PM1+PM2_Supporting+PM3+PM5+PP3).
CONCLUSIONS: The compound heterozygous variants of c.258+2T>C and c.100A>G probably underlay the SDS in this child. For children with refractory diarrhea, liver damage and growth retardation, SDS should be suspected, and genetic testing can facilitate the diagnosis and treatment.