目的 探讨1例纤维软骨增生1型(FBCG1)患儿的临床表型及遗传学特征。 方法 选取2021年1月21日因"重症肺炎、疑似先天性遗传代谢病"就诊于甘肃省妇幼保健院的1例FBCG1患儿作为研究对象。收集患儿的临床资料，提取患儿及其父母的外周血样DNA，进行全外显子组测序(WES)，用Sanger测序对候选变异进行家系验证。 结果 患儿为1月龄女性，存在面部畸形、骨骼发育异常及四肢内翻等表型。WES检测显示其携带COL11A1基因c.3358G>A/c.2295+1G>A复合杂合变异，相关疾病为纤维软骨增生症。上述变异分别遗传自表型正常的父亲和母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南，c.3358G>A变异符合判读PM1+PM2_Supporting+PM3+PP3，c.2295+1G>A变异符合判读PVS1+PM2_Supporting，二者均被判定为可能致病性变异。 结论 COL11A1基因c.3358G>A/c.2295+1G>A复合杂合变异可能是患儿的遗传学病因。上述发现对患儿的确诊、遗传咨询及其父母的再生育指导具有重要的意义。 Objective To analyze the clinical data and genetic characteristics of a child with fibrocartilage hyperplasia type 1 (FBCG1). Methods A child who was admitted to Gansu Provincial Maternity and Child Health Care Hospital on January 21, 2021 due to severe pneumonia and suspected congenital genetic metabolic disorder was selected as the study subject. Clinical data of the child was collected, and genomic DNA was extracted from peripheral blood samples from the child and her parents. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Results The patient, a 1-month-old girl, had presented with facial dysmorphism, abnormal skeletal development, and clubbing of upper and lower limbs. WES revealed that she has harbored compound heterozygous variants c. 3358G>A/c.2295+ 1G>A of theCOL11A1 gene, which has been associated with fibrochondrogenesis. Sanger sequencing has verified that the variants have been respectively inherited from her father and mother, both of whom were phenotypically normal. Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG), the c. 3358G>A variant was graded as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PP3), and so was the c. 2295+ 1G>A variant (PVS1+ PM2_Supporting). Conclusion The compound heterozygous variants c. 3358G>A/c.2295+ 1G>A probably underlay the disease in this child. Above finding has facilitated definite diagnosis, genetic counseling for her family.
Abstract
Objective To analyze the clinical data and genetic characteristics of a child with fibrocartilage hyperplasia type 1 (FBCG1). Methods A child who was admitted to Gansu Provincial Maternity and Child Health Care Hospital on January 21, 2021 due to severe pneumonia and suspected congenital genetic metabolic disorder was selected as the study subject. Clinical data of the child was collected, and genomic DNA was extracted from peripheral blood samples from the child and her parents. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Results The patient, a 1-month-old girl, had presented with facial dysmorphism, abnormal skeletal development, and clubbing of upper and lower limbs. WES revealed that she has harbored compound heterozygous variants c. 3358G>A/c.2295+ 1G>A of theCOL11A1 gene, which has been associated with fibrochondrogenesis. Sanger sequencing has verified that the variants have been respectively inherited from her father and mother, both of whom were phenotypically normal. Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG), the c. 3358G>A variant was graded as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PP3), and so was the c. 2295+ 1G>A variant (PVS1+ PM2_Supporting). Conclusion The compound heterozygous variants c. 3358G>A/c.2295+ 1G>A probably underlay the disease in this child. Above finding has facilitated definite diagnosis, genetic counseling for her family.
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