Atypical Alstrom syndrome with novel ALMS1 mutations precluded by current diagnostic criteria.

Hdl Handle:
http://hdl.handle.net/10147/322492
Title:
Atypical Alstrom syndrome with novel ALMS1 mutations precluded by current diagnostic criteria.
Authors:
Casey, Jillian; McGettigan, Paul; Brosnahan, Donal; Curtis, Emma; Treacy, Eileen; Ennis, Sean; Lynch, Sally Ann
Citation:
Atypical Alstrom syndrome with novel ALMS1 mutations precluded by current diagnostic criteria. 2014, 57 (2-3):55-9 Eur J Med Genet
Journal:
European journal of medical genetics
Issue Date:
Feb-2014
URI:
http://hdl.handle.net/10147/322492
DOI:
10.1016/j.ejmg.2014.01.007
PubMed ID:
24503146
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.
Language:
en
Keywords:
GENETICS; INFANT
ISSN:
1878-0849

Full metadata record

DC FieldValue Language
dc.contributor.authorCasey, Jillianen_GB
dc.contributor.authorMcGettigan, Paulen_GB
dc.contributor.authorBrosnahan, Donalen_GB
dc.contributor.authorCurtis, Emmaen_GB
dc.contributor.authorTreacy, Eileenen_GB
dc.contributor.authorEnnis, Seanen_GB
dc.contributor.authorLynch, Sally Annen_GB
dc.date.accessioned2014-07-07T10:47:00Z-
dc.date.available2014-07-07T10:47:00Z-
dc.date.issued2014-02-
dc.identifier.citationAtypical Alstrom syndrome with novel ALMS1 mutations precluded by current diagnostic criteria. 2014, 57 (2-3):55-9 Eur J Med Geneten_GB
dc.identifier.issn1878-0849-
dc.identifier.pmid24503146-
dc.identifier.doi10.1016/j.ejmg.2014.01.007-
dc.identifier.urihttp://hdl.handle.net/10147/322492-
dc.description.abstractWe 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to European journal of medical geneticsen_GB
dc.subjectGENETICSen_GB
dc.subjectINFANTen_GB
dc.titleAtypical Alstrom syndrome with novel ALMS1 mutations precluded by current diagnostic criteria.en_GB
dc.identifier.journalEuropean journal of medical geneticsen_GB
dc.description.fundingOtheren
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen

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