A novel lysozyme mutation Phe57Ile associated with hereditary renal amyloidosis

• Published in: Kidney international Vol. 63; no. 5; pp. 1652 - 1657
• Main Authors: Yazaki, Masahide, Farrell, Sandra A., Benson, Merrill D.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2003; Nature Publishing; Elsevier Limited
• Subjects: Amyloidosis; Amyloidosis - genetics; Amyloidosis - pathology; Biological and medical sciences; compound heterozygosity; European Continental Ancestry Group - genetics; Family Health; Female; hereditary amyloidosis; Humans; Kidney Diseases - genetics; Kidney Diseases - pathology; lysozyme variant; Medical sciences; Metabolic diseases; Middle Aged; Muramidase - genetics; nephropathy; Other metabolic disorders; Pedigree; Point Mutation; polymorphism; Polymorphism, Restriction Fragment Length; Polymorphism, Single-Stranded Conformational; hereditary amyloidosis; nephropathy; polymorphism; compound heterozygosity; lysozyme variant; Enzymopathy; Kidney; Female; Genetics; Lysozyme; Kidney disease; Human; Urinary system disease; Enzyme; Etiopathogenesis; Metabolic diseases; Hereditary; Protein; Genetic disease; Case study; Variant; Glycosidases; DNA; Renal failure; Hydrolases; Amyloidosis; Mutation; O-Glycosidases
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1046/j.1523-1755.2003.00904.x

A novel lysozyme mutation Phe57Ile associated with hereditary renal amyloidosis. Variant forms of lysozyme, a ubiquitous bacteriolytic enzyme, are known to lead to hereditary non-neuropathic renal amyloidosis and, so far, three different mutations of the lysozyme gene have been reported. In this study, we report a novel lysozyme variant, Phe57Ile, associated with renal amyloidosis in three patients in one Italian Canadian family. The proband was a 52-year-old woman who developed renal failure at the age of 42 years. Renal biopsy demonstrated replacement of glomeruli by amyloid. Her younger sister and her younger daughter who underwent renal transplantation also had renal amyloidosis. The proband's older daughter and her niece were in good health. To elucidate pathogenesis of this hereditary renal amyloidosis, DNA analyses of the lysozyme gene, including single strand confirmation polymorphism, direct DNA sequence, and restriction fragment length polymorphism analyses, were performed. DNA analyses of the lysozyme gene revealed a T to A transversion at the first position of codon 57 of the lysozyme gene in the proband, her sister, and her affected and unaffected daughters, indicating a replacement of Phe by Ile at residue 57. In addition, DNA sequencing demonstrated a C to A transversion at the second position of codon 70, denoting a replacement of Thr by Asn at residue 70, in the proband's sister and her niece. Thus, the proband's sister is compound heterozygous for the Phe57Ile and Thr70Asn alleles. Distinctive clinical features in patients of this family are nephropathy due to renal amyloidosis. Our results indicate that the novel lysozyme variant Phe57Ile is associated with renal amyloidosis in this family. From our results, a clear relation between the Thr70Asn polymorphism and renal amyloidosis could not be demonstrated.