title: Alström Syndrome: Mutation Spectrum of ALMS1.
abstract: Alström Syndrome (ALMS), a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically characterized by multisystem involvement including early cone-rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2 diabetes mellitus, cardiomyopathy, fibrosis, and multiple organ failure. The precise function of ALMS1 remains elusive, but roles in endosomal and ciliary transport and cell cycle regulation have been shown. The aim of our study was to further define the spectrum of ALMS1 mutations in patients with clinical features of ALMS. Mutational analysis in a world-wide cohort of 204 families identified 109 novel mutations, extending the number of known ALMS1 mutations to 239 and highlighting the allelic heterogeneity of this disorder. This study represents the most comprehensive mutation analysis in patients with ALMS, identifying the largest number of novel mutations in a single study worldwide. Here, we also provide an overview of all ALMS1 mutations identified to date.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine.|Alström Syndrome International, Mount Desert, Maine.
authors.forename: Jan D
authors.initials: JD
authors.lastname: Marshall
authors.affiliation: IGBMC, CNRS UMR 7104/INSERM U964/University of Strasbourg, Illkirch Cedex, France.|Laboratoire ICUBE, UMR CNRS 7357, LBGI, Université de Strasbourg, Strasbourg, France.|Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg Cedex, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Muller
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine.
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Collin
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Milan
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Kingsmore
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.|Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Darrell
authors.initials: D
authors.lastname: Dinwiddie
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Farrow
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Miller
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Favaretto
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Maffei
authors.affiliation: Laboratoire de Génétique médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine FMTS, Université de Strasbourg, Strasbourg, France.|Service de Génétique Médicale, Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine.
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Naggert
mesh_terms: D000293:Adolescent; D000328:Adult; D056769:Alstrom Syndrome / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D005091:Exons; D006801:Humans; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D011506:Proteins
keywords: ALMS1; Alström Syndrome; SNV; ciliopathy
references.citation: Eur J Clin Invest. 2007 Feb;37(2):99-105
references.pmid: 17217374
references.citation: Hum Genet. 2007 Jun;121(5):647
references.pmid: 17879439
references.citation: AJNR Am J Neuroradiol. 2015 Jan;36(1):160-5
references.pmid: 25355816
references.citation: World Psychiatry. 2011 Jun;10(2):86-92
references.pmid: 21633677
references.citation: Clin Endocrinol (Oxf). 2007 Feb;66(2):269-75
references.pmid: 17223998
references.citation: Diabetologia. 2003 Jul;46(7):1023-4
references.pmid: 12827243
references.citation: Ital J Pediatr. 2014 Apr 02;40(1):33
references.pmid: 24690487
references.citation: Arch Ophthalmol. 2008 Jan;126(1):51-7
references.pmid: 18195218
references.citation: Hum Genet. 2007 Jun;121(5):645
references.pmid: 17879432
references.citation: Orphanet J Rare Dis. 2007 Dec 21;2:49
references.pmid: 18154657
references.citation: Clin Genet. 2007 Oct;72(4):351-6
references.pmid: 17850632
references.citation: Bioinformatics. 2007 Nov 1;23(21):2947-8
references.pmid: 17846036
references.citation: PLoS One. 2014 Oct 09;9(10):e109540
references.pmid: 25299671
references.citation: Nat Genet. 2002 May;31(1):74-8
references.pmid: 11941369
references.citation: Eur J Hum Genet. 2014 Jan;22(1):140-3
references.pmid: 23652376
references.citation: Nucleic Acids Res. 2001 Jan 1;29(1):308-11
references.pmid: 11125122
references.citation: Kidney Int. 2011 Mar;79(6):691-692
references.pmid: 21358663
references.citation: Br J Dermatol. 2011 Apr;164(4):878-80
references.pmid: 21128906
references.citation: Hum Mutat. 2000;15(1):7-12
references.pmid: 10612815
references.citation: Eur J Hum Genet. 2013 Nov;21(11):
references.pmid: 23612576
references.citation: Mol Vis. 2013 Sep 07;19:1885-91
references.pmid: 24049434
references.citation: Eur J Med Genet. 2014 Feb;57(2-3):71-5
references.pmid: 24462884
references.citation: Clin Genet. 2013 Jan;83(1):96-8
references.pmid: 22533542
references.citation: Eur J Hum Genet. 2011 Apr;19(4):485-8
references.pmid: 21157496
references.citation: Mol Vis. 2013 Nov 24;19:2393-406
references.pmid: 24319333
references.citation: Ann Ital Med Int. 2002 Oct-Dec;17(4):221-8
references.pmid: 12532560
references.citation: Circ Cardiovasc Genet. 2013 Dec;6(6):569-78
references.pmid: 24122612
references.citation: Arch Intern Med. 2005 Mar 28;165(6):675-83
references.pmid: 15795345
references.citation: Hum Genet. 2001 Jul;109(1):121-4
references.pmid: 11479744
references.citation: Pediatrics. 2014 Mar;133(3):e780-3
references.pmid: 24534407
references.citation: Hum Mol Genet. 2005 Aug 15;14(16):2323-33
references.pmid: 16000322
references.citation: Nat Commun. 2014 Mar 04;5:3416
references.pmid: 24595103
references.citation: Am J Med Genet A. 2015 Apr;167A(4):886-90
references.pmid: 25706677
references.citation: Am J Hum Genet. 2011 Apr 8;88(4):440-9
references.pmid: 21457909
references.citation: PeerJ. 2015 Mar 03;3:e796
references.pmid: 25780760
references.citation: Eur J Med Genet. 2014 Feb;57(2-3):55-9
references.pmid: 24503146
references.citation: Eye (Lond). 2009 May;23(5):1210-2
references.pmid: 18654604
references.citation: PLoS Genet. 2007 Jan 5;3(1):e8
references.pmid: 17206865
references.citation: Sci Transl Med. 2012 Oct 3;4(154):154ra135
references.pmid: 23035047
references.citation: Nat Methods. 2010 Aug;7(8):575-6
references.pmid: 20676075
references.citation: Hum Mutat. 2011 Dec;32(12):1450-9
references.pmid: 21901789
references.citation: PLoS One. 2011 Apr 26;6(4):e19081
references.pmid: 21541333
references.citation: Clin Dysmorphol. 2013 Jan;22(1):7-12
references.pmid: 23188138
references.citation: Diabetes. 2005 May;54(5):1581-7
references.pmid: 15855349
references.citation: Eur J Med Genet. 2014 Sep;57(9):532-5
references.pmid: 24972238
references.citation: J Med Genet. 2012 Aug;49(8):502-12
references.pmid: 22773737
references.citation: Ophthalmic Genet. 2012 Mar;33(1):18-22
references.pmid: 22004009
references.citation: Nat Genet. 2011 May;43(5):491-8
references.pmid: 21478889
references.citation: Sci Transl Med. 2011 Jan 12;3(65):65ra4
references.pmid: 21228398
references.citation: Clin Genet. 2015 Feb;87(2):161-6
references.pmid: 24400638
references.citation: Int J Pediatr Otorhinolaryngol. 2014 Mar;78(3):530-6
references.pmid: 24485176
references.citation: Curr Genomics. 2011 May;12(3):225-35
references.pmid: 22043170
references.citation: Eur J Hum Genet. 2007 Dec;15(12):1193-202
references.pmid: 17940554
references.citation: Hum Mutat. 2007 Nov;28(11):1114-23
references.pmid: 17594715
references.citation: Mol Biol Cell. 2010 Nov 1;21(21):3617-29
references.pmid: 20844083
references.citation: Bioinformatics. 2010 Apr 1;26(7):873-81
references.pmid: 20147302
references.citation: PLoS One. 2012;7(5):e37925
references.pmid: 22693585
references.citation: Am J Med Genet A. 2009 Feb 15;149A(4):662-5
references.pmid: 19283855
references.citation: J Cell Sci. 2014 Jun 1;127(Pt 11):2407-19
references.pmid: 24681783
references.citation: BMC Pediatr. 2013 Aug 27;13:130
references.pmid: 23981649
references.citation: Hum Genet. 2012 Mar;131(3):407-13
references.pmid: 21877133
references.citation: J Med Genet. 2000 Jul;37(7):E8
references.pmid: 10882760
references.citation: Am J Med Genet. 1997 Dec 12;73(2):150-61
references.pmid: 9409865
references.citation: Diabetologia. 2006 Jun;49(6):1209-13
references.pmid: 16601972
references.citation: Nat Methods. 2010 Apr;7(4):248-9
references.pmid: 20354512
references.citation: J Med Genet. 2005 Feb;42(2):e10
references.pmid: 15689433
references.citation: Br J Ophthalmol. 2007 Jul;91(7):983-4
references.pmid: 17576719
references.citation: J Hum Genet. 2015 Jan;60(1):1-9
references.pmid: 25296579
references.citation: Kidney Int. 2014 Apr;85(4):880-7
references.pmid: 24257694
references.citation: Nat Genet. 2002 May;31(1):79-83
references.pmid: 11941370
references.citation: J Clin Endocrinol Metab. 2006 Aug;91(8):3110-6
references.pmid: 16720663
references.citation: BMJ Case Rep. 2011 Aug 17;2011:
references.pmid: 22688943
references.citation: Hum Genet. 2014 Jan;133(1):1-9
references.pmid: 24077912
references.citation: Expert Rev Mol Diagn. 2011 Nov;11(8):855-68
references.pmid: 22022947
references.citation: J Pediatr Endocrinol Metab. 2007 Sep;20(9):1045-52
references.pmid: 18038714
references.citation: Mol Vis. 2012;18:1794-802
references.pmid: 22876109
references.citation: Nat Protoc. 2009;4(7):1073-81
references.pmid: 19561590
references.citation: Clin Genet. 2004 Feb;65(2):156-7
references.pmid: 14984477