Alstrom Syndrome with Novel ALMS1 Mutations: A Case Report

Abstract

Objective To report novel mutations of ALMS1 and evaluate clinical characteristics in the Chinese Child with Alstrom syndrome (ALMS).

Methods The Child and his parents were examined clinically and venous blood was collected. ALMSl gene analysis was carried out using DNA Sanger sequencing. Using polymerase chain reaction (PCR) amplified ALMS1 gene exons and splice sequence. The objective products were directly sequenced and analyzed. Pathogenic gene mutations were identified by contrast with the transcript (GRCh37/hg19).

Results The Child had typical clinical features of Alstrom syndrome. Sequencing the ALMS1 gene confirmed 2 novel heterozygous non-sense mutations in exon8, c.4600C>T (p.Q1534X) and in exon16, c.11410C>T (p.R3804X), respectively, resulting in premature protein truncation.

Conclusions 2 novel heterozygous non-sense mutations were identified in the Chinese Child with Alstrom syndrome, expanding the ALMS1 gene mutations causing Alstrom syndrome.

• References

• 1 Marshall JD, Muller J, Collin GB. et al. Alstrom syndrome: Mutation spectrum of ALMS1. Human Mutation 2015; 36: 660-668
• 2 Alstrom CH, Hallgren B, NilssonL B. et al. Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness: A specific syndrome (not hitherto described) distinct from the Laurence-Moon-Bardet-Biedl syndrome: A clinical, endocrinological and gen-etic examination based on a large pedigree. Acta Psychiatr Neurol Scand Suppl 1959; 129: 1-35
• 3 Li G, Vega R, Nelms K. et al. A Role for Alstrom syndrome protein, alms1, in kidney ciliogenesis and cellular quiescenc. PLoS Genet 2007; 3: e8
• 4 Collin GB, Marshall JD, King BL. et al. The Alstrom syndrome protein, ALMS1, interacts with α-actinin and components of the endosome recycling pathway. PLoS One 2012; 7: e37925
• 5 Louw JJ, Corveleyn A, Jia Y. et al. Homozygous loss-of-function mutation in ALMS1 caues the lethal disorder mitogenic cardiomyopathy in two siblings. Eur J Med Gene-t 2014; 57: 532-535
• 6 Favaretto F, Milan G, Collin GB. et al. GLUT4 defects in adipose tissue are the earl-y signs of metabolic alterations in Alms1GT/GT, a mousemodel for obesity and insul-inresistance. PLoSOne 2014; 9: e109540
• 7 Leitch CC, Lodh S, Prieto-Echague V. et al. Basal body proteins regulate Notch signaling via endosomal trafficking. J Cell Sci 2014; 127: 2407-2419
• 8 Orphanet: an online rare disease and orphan drug data base [homepage on the Interne-t]. Paris: INSERM; 1997. [updatedNov2012]
• 9 Marshall DJ, Maffei P, Collin BG. et al. Alstrom syndrome: Genetics and clinical overview. Current Genomics 2011; 12: 225-235
• 10 Liu L, Dong B, Chen X. et al. Identification of a novel ALMS1 mutation in a Chinese family with Alstrom syndrome. Eye (Lond) 2009; 23: 1210-1212
• 11 Aoife MW, Philip LB. Ciliopathies: an expanding disease spectrum. Pediatric Nephrology 2011; 26: 1039-1056
• 12 Marshall JD, Beck S, Maffei P. et al. Alstrom Syndrome. European Journal of Human Genetics 2007; 15: 1193-1202
• 13 Mockel A, Obringer C, Hakvoort TB. Pharmacological modulation of the retinal-unfolded protein response in Bardet-Biedl syndrome reduces apoptosis and preserves light detection ability. J Biol Chem 2012; 287: 37483-37494
• 14 Patel V, Chowdhury R, Igarashi P. Advances in the pathogenesis and treatment of po-lycystic kidney disease. Current Opinion in Nephrology and Hypertension 2009; 18: 99-106
• 15 Chang MY, Ong AC. Mechanism-based therapeutics for autosomal dominant polycystic kidney disease: Recent progress and future prospects. Nephron. Clinical Practice 2012; 120: c25-c34