title: Complexities of Genetic Counseling for ALS: A Case of Two Siblings with Discordant Genetic Test Results.
abstract: Rapid advances in the genetics of amyotrophic lateral sclerosis (ALS) have dramatically changed the approach of clinicians and researchers to the motor neuron diseases. We report two siblings in whom the genetic study provided conflicting results, hence raising a number of issues which deserve to be considered by clinicians involved in genetic testing for ALS. The first patient died within 2 years of ALS onset, while her brother still manages to walk unaided, 7 years into onset. Genetic analyses, performed on the first patient as part of a research protocol, and as clinical genetic testing on the brother, provided different results. Results for Patient 1 were negative for all investigated genes, thus suggesting that her disease may be a phenocopy, while her brother carried an autosomal dominant TARDBP mutation (p.A382T). A multidisciplinary approach may help patients and clinicians face the emerging dilemmas in such a complex field. Sharing and updating of advances, not to mention uncertainties inherent to current knowledge, with patients and families may prove to be an effective way to support them and to make them aware of the present limits of our knowledge and of the blurred border between research and clinical practice.
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genova, Viale Benedetto XV, 6, 16132, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mandich
authors.forename: Vittorio
authors.initials: V
authors.lastname: Mantero
authors.forename: Simonetta
authors.initials: S
authors.lastname: Verdiani
authors.forename: Fabio
authors.initials: F
authors.lastname: Gotta
authors.forename: Claudia
authors.initials: C
authors.lastname: Caponnetto
authors.forename: Emilia
authors.initials: E
authors.lastname: Bellone
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ferrandes
authors.forename: Paola
authors.initials: P
authors.lastname: Origone
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000517:prevention & control; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005817:Genetic Counseling / Q000379:methods*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D035781:Siblings
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human
references.citation: Arch Neurol. 2011 May;68(5):594-8
references.pmid: 21220647
references.citation: Clin Genet. 2013 May;83(5):408-16
references.pmid: 23379621
references.citation: Neurogenetics. 2013 May;14(2):161-6
references.pmid: 23546887
references.citation: J Neurol Neurosurg Psychiatry. 2012 Apr;83(4):365-7
references.pmid: 22399794
references.citation: Pract Neurol. 2015 Feb;15(1):80-4
references.pmid: 25169240
references.citation: Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9
references.pmid: 11464847
references.citation: J Neurol Neurosurg Psychiatry. 2010 May;81(5):572-7
references.pmid: 20460594
references.citation: Neuron. 2011 Oct 20;72(2):257-68
references.pmid: 21944779
references.citation: Trends Neurosci. 2014 Aug;37(8):433-42
references.pmid: 24927875
references.citation: Hum Mutat. 2009 Apr;30(4):688-94
references.pmid: 19224587
references.citation: Nat Rev Neurol. 2011 Oct 11;7(11):603-15
references.pmid: 21989245
references.citation: J Neurol Neurosurg Psychiatry. 2014 May;85(5):478-85
references.pmid: 23833266
references.citation: Hum Mol Genet. 2012 Sep 1;21(17):3776-84
references.pmid: 22645277