BACKGROUND AND OBJECTIVES: Alport syndrome (AS) is a predominantly X-linked hereditary nephritis associated with high-tone, sensorineural deafness and characteristic eye signs. Clinical diagnostic criteria were defined in 1988. Most cases result from mutations in the X-linked collagen gene COL4A5, with mutations in the autosomal genes COL4A3 and COL4A4 on chromosome 2 accounting for the rest. Mutation analysis of COL4A5 with a combination of sequencing and multiplex ligation-dependent probe amplification has been available for several years. The objective of this study was to determine the utility of clinical diagnostic criteria in identifying patients likely to have a COL4A5 mutation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical information was available on 206 patients whose DNA was received for testing between 1994 and June 2008; predictive tests for a known familial mutation, samples from duplicate family members, and incompletely screened samples were excluded. One hundred and twenty-eight patients (62.1%) had a pathogenic COL4A5 mutation. RESULTS: The mutation detection rate in families fulfilling zero, one, two, three, or four diagnostic criteria was 0%, 18%, 64%, 89%, and 81%, respectively. Sixty-seven percent of patients with COL4A5 mutations meeting only two diagnostic criteria had not had a complete clinical assessment. In two thirds of families meeting four diagnostic criteria without an identified COL4A5 mutation, autosomal inheritance was confirmed or suspected. CONCLUSIONS: The authors recommend COL4A5 analysis in any patient meeting at least two clinical diagnostic criteria. COL4A3 and COL4A4 analysis should be considered if a COL4A5 mutation is not detected and primarily if autosomal inheritance is suspected.
BACKGROUND AND OBJECTIVES:Alport syndrome (AS) is a predominantly X-linked hereditary nephritis associated with high-tone, sensorineural deafness and characteristic eye signs. Clinical diagnostic criteria were defined in 1988. Most cases result from mutations in the X-linked collagen gene COL4A5, with mutations in the autosomal genes COL4A3 and COL4A4 on chromosome 2 accounting for the rest. Mutation analysis of COL4A5 with a combination of sequencing and multiplex ligation-dependent probe amplification has been available for several years. The objective of this study was to determine the utility of clinical diagnostic criteria in identifying patients likely to have a COL4A5 mutation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical information was available on 206 patients whose DNA was received for testing between 1994 and June 2008; predictive tests for a known familial mutation, samples from duplicate family members, and incompletely screened samples were excluded. One hundred and twenty-eight patients (62.1%) had a pathogenic COL4A5 mutation. RESULTS: The mutation detection rate in families fulfilling zero, one, two, three, or four diagnostic criteria was 0%, 18%, 64%, 89%, and 81%, respectively. Sixty-seven percent of patients with COL4A5 mutations meeting only two diagnostic criteria had not had a complete clinical assessment. In two thirds of families meeting four diagnostic criteria without an identified COL4A5 mutation, autosomal inheritance was confirmed or suspected. CONCLUSIONS: The authors recommend COL4A5 analysis in any patient meeting at least two clinical diagnostic criteria. COL4A3 and COL4A4 analysis should be considered if a COL4A5 mutation is not detected and primarily if autosomal inheritance is suspected.
Authors: F T van der Loop; L A Monnens; C H Schröder; H H Lemmink; M H Breuning; E D Timmer; H J Smeets Journal: Kidney Int Date: 1999-04 Impact factor: 10.612
Authors: I Naito; S Nomura; S Inoue; M Kagawa; T Matsubara; T Araki; M Taki; H Ohmori; K Manabe; S Kawai; G Osawa; Y Sado Journal: Contrib Nephrol Date: 1997 Impact factor: 1.580
Authors: P Martin; N Heiskari; J Zhou; A Leinonen; T Tumelius; J M Hertz; D Barker; M Gregory; C Atkin; U Styrkarsdottir; H Neumann; J Springate; T Shows; E Pettersson; K Tryggvason Journal: J Am Soc Nephrol Date: 1998-12 Impact factor: 10.121
Authors: Judy Savige; Elisabet Ars; Richard G H Cotton; David Crockett; Hayat Dagher; Constantinos Deltas; Jie Ding; Frances Flinter; Genevieve Pont-Kingdon; Nizar Smaoui; Roser Torra; Helen Storey Journal: Pediatr Nephrol Date: 2013-05-30 Impact factor: 3.714