👤 Mariluce Riegel

Few patients with interstitial deletions in the distal long arm of chromosome 14 have been reported, and these patients showed rather indistinct features, including growth and mental retardation and phenotypic alterations. We describe a de novo 14q interstitial deletion in a 6-year-old boy with dysmorphic facial traits such as hypertelorism, short and narrow palpebral fissures, broad nose with anteverted nostrils, long philtrum, thin upper lip with cupid's bow, prominent and everted lower lip, mildly low-set ears, as well as moderate developmental delay and mild mental retardation. Array-CGH mapped the deletion to the region 14q24.3 to 14q31.3, including 13.11 Mb, proximal to the imprinted genomic region of 14q32. This mild phenotypic presentation suggests that the deleted segment does not contain essential genes for early organ development. Twenty-two genes with known functions, including Neurexin III (NRXN3, OMIM 600567), map to the region deleted in the propositus. Show less

Long-term observations of individuals with the so-called Langer-Giedion (LGS) or tricho-rhino-phalangeal type II (TRPS2) are scarce. We report here a on follow-up of four LGS individuals, including one first described by Andres Giedion in 1969, and review the sparse publications on adults with this syndrome which comprises ectodermal dysplasia, multiple cone-shaped epiphyses prior to puberty, multiple cartilaginous exostoses, and mostly mild intellectual impairment. LGS is caused by deletion of the chromosomal segment 8q24.11-q24.13 containing among others the genes EXT1 and TRPS1. Most patients with TRPS2 are only borderline or mildly cognitively delayed, and few are of normal intelligence. Their practical skills are better than their intellectual capability, and, for this reason and because of their low self-esteem, they are often underestimated. Some patients develop seizures at variable age. Osteomas on processes of cervical vertebrae may cause pressure on cervical nerves or dissection of cerebral arteries. Joint stiffness is observed during childhood and changes later to joint laxity causing instability and proneness to trauma. Perthes disease is not rare. Almost all males become bald at or soon after puberty, and some develop (pseudo) gynecomastia. Growth hormone deficiency was found in a few patients, TSH deficiency so far only in one. Puberty and fertility are diminished, and no instance of transmission of the deletion from a non-mosaic parent to a child has been observed so far. Several affected females had vaginal atresia with consequent hydrometrocolpos. Show less

It has not been established firmly whether dyslipidemia contributes independently to the progression of kidney disease. Lipid and lipoprotein parameters, including levels of total, HDL, and LDL cholesterol; triglycerides; lipoprotein(a); apolipoprotein A-IV; and the apolipoprotein E and A-IV polymorphisms, were assessed in 177 patients who had mostly mild to moderate renal insufficiency and were followed prospectively for up to 7 yr. Progression of kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure necessitating renal replacement therapy. In univariate analysis, patients who reached a progression end point (n = 65) were significantly older and had higher serum creatinine and proteinuria as well as lower GFR and hemoglobin levels. In addition, baseline apolipoprotein A-IV and triglyceride concentrations were higher and HDL cholesterol levels were lower. Multivariate Cox regression analysis revealed that baseline GFR (hazard ratio 0.714; 95% confidence interval [CI] 0.627 to 0.814 for an increment of 10 ml/min per 1.73 m(2); P < 0.0001) and serum apolipoprotein A-IV concentrations (hazard ratio 1.062; 95% CI 1.018 to 1.108 for an increment of 1 mg/dl; P = 0.006) were significant predictors of disease progression. Patients with apolipoprotein A-IV levels above the median had a significantly faster progression (P < 0.0001), and their mean follow-up time to a progression end point was 53.7 mo (95% CI 47.6 to 59.8) as compared with 70.0 mo (95% CI 64.6 to 75.4) in patients with apolipoprotein A-IV levels below the median. For the apolipoprotein E polymorphism, only the genotype epsilon2/epsilon4 was associated with an increased risk for progression. In summary, this prospective study in patients with nondiabetic primary kidney disease demonstrated that apolipoprotein A-IV concentration is a novel independent predictor of progression. Show less

Cell culture studies and investigations in mice that overexpress either human or mouse apolipoprotein A-IV (apoA-IV) revealed anti-atherogenic properties of apoA-IV. An association between low apoA-IV concentrations and coronary artery disease in humans was demonstrated; therefore, apoA-IV may also play an antiatherogenic role in humans. Because apoA-IV is markedly elevated in dialysis patients, patients with the earliest and modest stages of renal impairment were studied to assess the association of apoA-IV with GFR and atherosclerotic complications. GFR was measured by the use of iohexol in 227 non-nephrotic patients with different degrees of renal impairment. ApoA-IV increased significantly with decreasing GFR and was already elevated in earliest stages of renal disease (GFR > 90 ml/min per 1.73 m2). Multiple linear regression analysis identified renal function parameters (GFR, creatinine, and urea) as the most important determinants of apoA-IV levels in serum of these patients. Twenty-six patients had already experienced 36 atherosclerotic events. Logistic regression analysis identified three variables associated with atherosclerotic complications: age, apoA-IV, and gender. Each 1 mg/dl increase of apoA-IV decreased the odds ratio for an atherosclerotic complication by 8% (P = 0.011). The data clearly show that the anti-atherogenic apoA-IV starts to increase during the earliest phases of renal insufficiency, which makes apoA-IV an early marker of renal impairment. Show less