Kodra Neslida, Diamonstein Callie, Hauser Natalie S
Inova Translational Medicine Institute, Inova Fairfax Hospital, Virginia.
Mol Genet Genomic Med. 2019 May;7(5):e648. doi: 10.1002/mgg3.648. Epub 2019 Mar 27.
A family with skeletal and craniofacial anomalies is presented. Whole-exome sequencing (WES) analysis indicated a diagnosis of Larsen syndrome, although their clinical presentation does not include the hallmark joint dislocations typically observed in Larsen syndrome.
Patient consent for the sharing of de-identified clinical and genetic information, along with use of photographs for publication, was obtained. WES and variant segregation analysis by WES were performed by commercial laboratory, GeneDx (Gaithersburg, MD), on peripheral blood samples from the proband, her brother, and her parents using methods detailed on their website for test XomeDx Whole Exome Sequencing Trio (https://www.genedx.com/test-catalog/available-tests/xomedx-whole-exome-sequencing-trio/). WES uses next-generation sequencing (NGS) technology to assess for variants within the coding regions, or exons, of approximately 23,000 genes. For the FLNB gene (NM_001457.3), 100% of the coding region was covered at a minimum of 10x. GeneDx uses Sanger sequencing to confirm NGS variants.
WES revealed a heterozygous pathogenic variant, p.Glu227Lys (c.679G>A), in the FLNB gene in three out of the four family members tested. This variant is associated with Larsen syndrome, a skeletal dysplasia condition with a wide range of phenotypic variability that usually includes congenital joint dislocations.
This is a highly unusual presentation of Larsen syndrome in which the identifying hallmark trait is absent in the patients' phenotypes.
本文介绍了一个患有骨骼和颅面异常的家族。全外显子组测序（WES）分析表明该家族患有拉森综合征，尽管他们的临床表现并不包括拉森综合征中常见的标志性关节脱位。
已获得患者对共享去识别化临床和遗传信息以及使用照片用于发表的同意。商业实验室GeneDx（马里兰州盖瑟斯堡）使用其网站上针对XomeDx全外显子组测序三人组测试（https://www.genedx.com/test-catalog/available-tests/xomedx-whole-exome-sequencing-trio/）详细描述的方法，对先证者、她的哥哥及其父母的外周血样本进行WES和通过WES进行的变异分离分析。WES使用下一代测序（NGS）技术来评估大约23,000个基因的编码区域或外显子内的变异。对于FLNB基因（NM_001457.3），100%的编码区域至少被10倍覆盖。GeneDx使用桑格测序来确认NGS变异。
WES在四个测试家族成员中的三个中发现FLNB基因存在杂合致病性变异p.Glu227Lys（c.679G>A）。该变异与拉森综合征相关，拉森综合征是一种骨骼发育异常疾病，具有广泛的表型变异性，通常包括先天性关节脱位。
这是拉森综合征一种非常不寻常的表现形式，患者的表型中不存在该疾病的标志性特征。
