Journal Article


Donal Brosnahan
Paul A. McGettigan
Jillian Casey
Eileen Treacy



hearing loss cardiomyopathy dilated alms1 genotype phenotype correlations alstr m syndrome autosomal recessive dilated cardiomyopathy criteria cone rod dystrophy diagnostic exome human genetics diagnostic testing current

Atypical Alstrom syndrome with novel ALMS1 mutations precluded by current diagnostic criteria (2014)

Abstract We report on clinical and genetic studies in a non-consanguineous Irish sib-pair with infantile dilated cardiomyopathy and retinopathy. A diagnosis of Alström Syndrome (AS) was considered and diagnostic testing pursued. The Alströms gene (ALMS1) is very large (23 exons) and diagnostic testing of mutational hotspots (exon 6, 8 and 10) was negative. Furthermore the siblings were tall and did not have the typical phenotype of nystagmus, photophobia, obesity or hearing loss and so the AS diagnosis was removed. We then sought to identify the causative gene in this family using whole exome sequencing. Unexpectedly, the exome analysis identified novel compound heterozygous ALMS1 mutations in exon 5 (c.777delT:p.D260fs*26) and exon 20 (c.12145_12146insC:p.S4049fs*36) that segregated with the phenotype. Although the siblings show some clinical overlap with AS, their phenotype is not classical. It is plausible that their atypical presentation may be due to the location of the ALMS1 mutations outside the usual mutational hotspots. Our findings show how atypical cases of AS may be missed under the current diagnostic guidelines and support consideration of complete ALMS1 sequencing in children with two or more features, even if all of the core clinical features of AS are not present.
Collections Ireland -> University College Dublin -> Biomolecular and Biomedical Science Research Collection
Ireland -> Trinity College Dublin -> Paediatrics
Ireland -> Trinity College Dublin -> Paediatrics (Scholarly Publications)
Ireland -> University College Dublin -> College of Science
Ireland -> University College Dublin -> School of Biomolecular & Biomedical Science
Ireland -> Trinity College Dublin -> School of Medicine

Full list of authors on original publication

Donal Brosnahan, Paul A. McGettigan, Jillian Casey, Eileen Treacy

Experts in our system

Paul A. McGettigan
University College Dublin
Total Publications: 46
Jillian Casey
University College Dublin
Total Publications: 24
Eileen Treacy
University College Dublin
Total Publications: 18