Abstract
Purpose :
Alström syndrome (AS) is a rare monogenic ciliopathy disorder with features including cone-rod dystrophy, sensory neural hearing loss, metabolic dysfunctions and multiple organ failure caused by bi-allelic mutations in a centrosomal basal body protein-coding gene known as ALMS1. We present a consanguineous Tunisian family with two affected members and a novel mutation.
Methods :
We performed a clinical and molecular genetic study of a consanguineous Tunisian family with two patients presenting retinal dystrophy, truncal obesity and sensorineural hearing loss.
Results :
Our patients had hemeralopia and visual loss from the second decade of life. Fundus examination showed retinal dystrophy with macular atrophy and peripheral spicule deposits. Mutation analysis after WES revealed a novel homozygous frameshift mutation c.281dupC, p.Q95Afs*32 in exon 1 in ALMS1.
Conclusions :
We describe a new ALMS1 mutation characterized by retinal dystrophy, truncal obesity, SNHL, without endocrine symptoms, neurological symptoms, hepatic symptoms, and renal Involvement. These findings are comparable to data reported in the literature. This alteration was not reported in the 1000 Genome Project or in the gnomAD database. This mutation is classified as pathogenic according to the American College of Medical Genetics (ACMG) guideline. This mutation expands the mutation spectrum of ALMS1 and helps to further study molecular pathogenesis of AS.
This is a 2020 ARVO Annual Meeting abstract.