Alström syndrome: A rare cause of dilated cardiomyopathy in five Chinese children.

Backgroud: The ALMS1 gene is predominantly localized to cilia, particularly in the photoreceptor cells of the retina, auditory neurons, kidneys, and other ciliated structures. Pathogenic mutations in this gene cause Alstrom syndrome (AS), which is characterized by dilated cardiomyopathy, retinal degeneration, neurodeafness, and centripetal obesity. However, the genetic mechanism of the ALMS1 gene remains unclear. This study reports five cases of Chinese children with heterozygous variants in the ALMS1 gene, aiming to expand the genetic map of AS and provide insights into its pathogenesis.

Methods: Whole exome sequencing (WES) was performed on 128 children diagnosed with DCM. ALMS1 variants were identified, and their pathogenicity and conservation were analyzed using bioinformatics tools. A retrospective analysis of genotypephenotype associations was also conducted in conjunction with previously reported cases.

Results: A total of eleven variants were identified in the five patients, including seven nonsense variants c.2035C > T(p.R679*), c.10825C > T(p.(R3609*)), c.5230C > T(p.(Q1744*)), c.3008C > A(p.(S1003*)), c.11686delG(p.(V3896*)), c.2090C > A(p.(S697*)), c.12373C > T(p.(Q4125*)), two frameshift variants c.10383delT(p.(I3461fs*48)), c.1685_c.1686insCAG(p.(D563fs*4)), and two missense variants c.12163C > G(p.(R4055G)) and c.7867G > A(p.A2623T). Cardiac ultrasound revealed improvements in left ventricular ejection fraction (LVEF) following treatment, although no significant change in nystagmus was observed.

Conclusions: This study expands the genetic spectrum of ALMS1 gene variants and reinforces their pathogenicity through bioinformatics analysis. Additionally, we emphasize the importance of comprehensive cardiac evaluation and genetic testing in patients with DCM presenting with nystagmus.