Objective To identify the pathogenic genetic variation of a family with pseudoxanthoma elasticum (PXE) and analyze its clinical phenotypic characteristics. Methods A retrospective clinical study. In July 2023, a PXE family was diagnosed through genetic testing at Henan Eye Hospital. A total of 5 members (including 1 proband and 4 family members) were included in the study. Detailed medical histories and family histories of the proband were collected, and visual acuity, fundus color photography, optical coherence tomography angiography (OCTA), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), electrocardiogram, cardiac color ultrasound and dermatological examinations were performed. Peripheral venous blood was collected from the proband and 4 family members, and genomic DNA was extracted. Whole exome sequencing was performed on the proband to screen for pathogenic genes. Sanger sequencing and real-time fluorescent quantitative polymerase chain reaction (qPCR) were used to verify the variations in the other family members. The pathogenicity grades of all variant sites were evaluated according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). AnnotSV software was used to annotate and analyze the detected copy number variations. Results The proband (Ⅱ-1), a 43-year-old female, impaired binocular vision for over a month. Her visual acuity was measured at 0.3 in the right eye and 0.2 in the left eye, with no improvement achievable through corrective measures. Intraocular pressure was within normal limits, and the anterior segment examination revealed no significant abnormalities. Color fundus photography showed that the optic discs of both eyes emitted multiple radial red-brown bands, with a mild "orange peel-like" change on the temporal side of the macula, and the right eye also had macular hemorrhage. The OCTA B scan image showed that the retina in the macular area was thickened, with strong reflective signals below the neuroepithelial layer, and abnormal blood flow signals were observed in the outer layer of the retina; the FFA combined with ICGA examination revealed choroidal neovascularization in the macular area and vascular-like stripes around the optic disc. The skin examination showed that the skin of both hands was thickened, with poor elasticity and laxity, and yellowish-nodular rashes were distributed in clusters on both sides of the neck. The clinical phenotype of the proband was in accordance with the diagnostic criteria of PXE, and no obvious clinical abnormalities were found in the other family members. Whole exome sequencing revealed that the proband carried a homozygous splice site variant of ABCC6 gene at c.1944-1G>A; Sanger sequencing verified that the mother (Ⅰ-2) was a heterozygous carrier of this site, while the husband (Ⅱ-2) and the two sons (Ⅲ-1, Ⅲ-2) were wild-type. The genotypes and disease phenotypes of the family were co-segregated. According to ACMG guidelines, the c.1944-1G>A variant was classified as pathogenic. Additionally, copy number vairations annotation analysis revealed a deletion of approximately 1.67 Mb at chr16:14818174-16487780 on chromosome 16 in the proband. This region includes genes such as MYH11, ABCC6, and NDE1, which were cataloged in OMIM database and completely overlap with the known pathogenic 16p13.11 microdeletion region. qPCR validation corroborated a significant reduction in the expression levels of the MYH11, ABCC6, and NDE1 genes in both the proband and her offspring, aligning with the observed copy number deletion. The husband was identified as wild-type, with no significant alterations in gene expression levels. The variations c.1944-1G>A and the 16p13 microdeletion were newly documented mutations. Conclusions The compound heterozygous variants in the ABCC6 gene, comprising the splice site variant c.1944-1G>A and the 16p13.11 microdeletion, underlie the autosomal recessive inheritance of PXE in this pedigree; both variants are novel and have not been previously reported.

Citation： Guo Haoyi, Jiang Yongqiang, Han Jinfeng. Investigation of the correlation between ABCC6 gene variation and clinical phenotype of pseudoxanthoma elasticum within a family. Chinese Journal of Ocular Fundus Diseases, 2026, 42(9): 756-763. doi: 10.3760/cma.j.cn511434-20250519-00218 Copy

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