Receiver operating curve analyses of urinary titin of healthy 3-y-old children may be a noninvasive screening method for Duchenne muscular dystrophy

Identification of marker proteins of muscular dystrophy in the urine proteome from the mdx-4cv model of dystrophinopathy

“…3 and illustrates the differential expression pattern of changed proteins in wild type versus the dystrophic phenotype. Increased levels of the giant muscle protein titin in mdx-4cv urine, as previously reported in dystrophic patients and the conventional mdx-23 mouse, [36][37][38][39][40][41] were clearly confirmed (Table 1). The proteomic screening study by Rouillon et al, 36 which was carried out with urine samples from 5 Duchenne patients and 5 healthy subjects, lists 8 increased proteins (titin, uromodulin, nuclear transport factor NTF2, TNF receptor, myosin-1, fibulin-2, complement Clr, aminopeptidase) and 2 decreased proteins (cubulin, beta-galactosidase).…”

“…30 The drastic elevation of urinary titin fragments was confirmed by immunoassays [37][38][39] and suggests that these protein species have a high potential as novel diagnostic markers and noninvasive screening tools. 21,40,41 Building on these findings, it was of interest to carry out a comprehensive proteomic comparison of urine and evaluate the body-wide effects of the dystrophic phenotype. In this report, we have used the established genetic mdx-4cv model of Duchenne muscular dystrophy, [42][43][44] which allows detailed comparisons of changes in the urine proteome due to primary or secondary pathological alterations in the dystrophic phenotype.…”

A sandwich ELISA kit reveals marked elevation of titin N‐terminal fragment levels in the urine of mdx mice

“…The fold change was similar to that observed in child patients with DMD 14 . In humans, studies on urinary titin have been accelerated by the introduction of an ELISA kit to measure human titin N‐terminal fragment levels (the human titin N‐fragment ELISA kit) 14,17–22 . As a result, high urinary titin levels have been identified in association with not only diseases 23 but also physical activities 23 .…”

Assessment of catabolic state in infants with the use of urinary titin N-fragment

“…These levels were higher than the average urinary level of titin N-fragment of healthy 3-year-old children: 2.2 ± 4.1 pmol/mg Cr. 24 Surprisingly, the increased level after birth was almost equivalent to that of the median level in patients with Becker muscular dystrophy: 43.4 pmol/mg Cr 20 or the peak of critically ill adults: 67.9 (35.7-116.2 pmol/mg Cr). 21 Given that the urinary titin N-fragment reflects muscle breakdown, 21 these results indicate that infants during the early postmenstrual age are exposed to an increased catabolism and subsequent muscle breakdown.…”