Work

Case Report: Sengers syndrome caused by a novel 7.6 kb AGK deletion misdiagnosed as isolated congenital cataract

Year: 2026

Type: article

Abstract: The diagnosis of Sengers syndrome, a rare mitochondrial disorder, is often challenged by phenotypic mimicry. We report a diagnostically instructive case of a 4-month-old female who presented with the classic triad of congenital cataracts, hypertrophic cardiomyopathy, and lactic acidosis. Initial whole-exome sequencing (WES) was confounded by the finding of a heterozygous variant in CRYBA2 and only a single heterozygous nonsense mutation in AGK (c.409C>T, p.Arg137*). The persistence of a multisystemic phenotype inconsistent with an isolated cataract disorder prompted further investigation. Copy number variation (CNV) analysis of the WES data revealed a large heterozygous deletion in AGK , which breakpoint-specific polymerase chain reaction and Sanger sequencing precisely characterized as a novel 7.6 kb deletion (chr7:141297542-141305156). This confirmed compound heterozygosity, yielding a definitive diagnosis of Sengers syndrome and reclassifying the CRYBA2 variant as incidental. Crucially, breakpoint analysis indicated a non-Alu-mediated mechanism for the deletion. This case highlights the critical importance of CNV analysis in resolving genetically ambiguous autosomal recessive cases and provides novel insight into the structural mutational landscape of AGK .

Source: Frontiers in Pediatrics

DOI: 10.3389/fped.2026.1714952

Authors: Xingwang Gong, Yue Liu, Hui Liang

Institutions: Fujian Medical University, First Affiliated Hospital of Fujian Medical University, Hainan General Hospital, Hainan Medical University

Language: English

Topic: Genomics and Rare Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801