Clinical and genetic analysis of a child with Spondyloocular syndrome due to compound heterozygous variants of XYLT2 gene

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To explore the clinical characteristics and genetic etiology of a child with Spondyloocular syndrome (SOS) in order to enhance the awareness and understanding of this disease. A 3.5-year-old boy with SOS who had presented at the Department of Medical Genetics of Hunan Children's Hospital on August 10, 2023 due to the repeated fractures for over 2 years and after binocular cataract surgery was selected as the study subject. Clinical data of his pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA and subjected to trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing and analyzed with bioinformatic software. This study was approved by the Medical Ethics Committee of Hunan Children's Hospital (Ethics No. KYAQ2022-263). The child had manifested repeated fractures, bilateral bowed femur, osteoporosis, cataract, atrial septal defect, and developmental delay. Ultrasonography has revealed fetal edema, peritoneal effusion, pleural effusion and polyhydramnios. Trio-whole exome sequencing and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XYLT2 gene, namely c.1103_1104delAG (p.Gln368Argfs*8) and c.1238_1253delinsA (p.Val413_Pro418delinsGlu), which were inherited from his phenotypically normal father and mother, respectively. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and recommendations from the Clinical Genome Resource (ClinGen), the c.1103_1104delAG was predicted as a pathogenic variant (PVS1+PM2_Supporting+PP4), whilst the c.1238_1253delinsA was predicted as a likely pathogenic variant (PM4+PM3+PM2_Supporting+PP4). The c.1103_1104delAG and c.1238_1253delinsA compound heterozygous variants of the XYLT2 gene probably underlay the pathogenesis in this child. Above finding has enriched the phenotypic and mutational spectrum of SOS, and provided a basis for the clinical diagnosis, treatment, prognosis assessment and genetic counseling for this pedigree.