Klinische Befunde eines Patienten mit Lowe-Syndrom und einer Splice Site Mutation im OCRL1-Gen

Keilhauer, Claudia N.; Gál, A.; Sold, J.; Zimmermann, Julien; Netzer, Kai‐Olaf; Schramm, Lisa

doi:10.1055/s-2007-962947

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…Hichri et al [22] reported two mutations (p.Ile274Thr, p.Arg318Cys) that have been associated with mild Lowe syndrome (Dent-2 disease) [8,9,12,55,56] but can also cause the severe phenotype even within the same family. A premature termination mutation (p.Gln199X) and a splice variant (IVS19+1G>A) were found to be associated with Lowe syndrome at patient's ages of 13 yr and 29 yr, respectively [10,57]. Both these cases had remained undiagnosed due to absence of congenital cataract or even any ocular involvement [10,57].…”

Section: Genotype-phenotype Correlationmentioning

confidence: 99%

“…A premature termination mutation (p.Gln199X) and a splice variant (IVS19+1G>A) were found to be associated with Lowe syndrome at patient's ages of 13 yr and 29 yr, respectively [10,57]. Both these cases had remained undiagnosed due to absence of congenital cataract or even any ocular involvement [10,57]. On the other hand, only minimal signs of tubular dysfunction and a mild behavioral and cognitive phenotype were found in association with an OCRL p.Glu851X nonsense mutation and a mild renal phenotype was also described due to an c.1244+5G>A defect [58,59].…”

Section: Genotype-phenotype Correlationmentioning

confidence: 99%

“…More mildly affected (Dent-2 disease) patients may show no pathologic findings but discrete peripheral opacity between nucleus and cortex, as well as mild bilateral nuclear sclerosis have been observed [11]. As mentioned above, Lowe syndrome may remain undiagnosed due to absence of congenital cataract or even any ocular involvement [10,57]. Studies of several Lowe syndrome patients have shown a wide range of heterogeneity in the white matter changes ranging from diffuse high-intensity signal to no demonstrable changes at all.…”

Section: Eyementioning

confidence: 99%

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Lowe syndrome/Dent-2 disease: A comprehensive review of known and novel aspects

2015

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The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, cognitive and behavioral impairment and a renal proximal tubulopathy in almost all of the patients. Whereas the ocular manifestations and severe hypotonia are present at birth, the renal involvement appears within the first months of life. Patients show progressive growth retardation and may develop a debilitating arthropathy. Treatment is symptomatic and life span rarely exceeds 40 yr. The causative OCRL gene, encodes an inositol polyphosphate 5-phosphatase. OCRL mutations were not only found in classic Lowe syndrome, but also in milder affected patients, classified as having Dent-2 disease. There is a phenotypic continuum within patients with Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for loss of enzyme function. Researchers have conducted a large amount of work to understand the etiology responsible for the disease. However, the mechanisms leading to the clinical manifestations are still poorly understood and we are far from an effective therapy. In this review, we have included well-established findings and the most recent progress in understanding Lowe syndrome and Dent-2 disease.

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Section: Genotype-phenotype Correlationmentioning

confidence: 99%

Section: Genotype-phenotype Correlationmentioning

confidence: 99%

Section: Eyementioning

confidence: 99%

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Lowe syndrome/Dent-2 disease: A comprehensive review of known and novel aspects

2015

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“…Typically complete opacification and discoid deformation of the lenses (microphakia) are seen, indicating a developmental defect in early embryogenesis ( Figure 2). Patients with mild Lowe syndrome phenotype may show incomplete lenticular opacities without visual impairment [6].…”

Section: Journal Of Genetic Syndromes and Gene Therapymentioning

confidence: 99%

Dismetabolic Cataracts: Clinicopathologic Overview and Surgical Management with B-MICS Technique

GM¹

2013

J Genet Syndr Gene Ther

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Background: Dismetabolic cataract is a loss of lens transparency due to an insult to the nuclear or lenticular fibers, caused by a metabolic disorder. The lens opacification may occur early or later in life, and may be isolated or associated to particular syndromes. We describe some of these metabolic conditions associated with cataract formation, and in particular we report our experience with a patient affected by lathosterolosis that presented bilateral cataracts. Methods: Our patient was a 7-years-old little girl diagnosed with lathosterolosis at age 2 years, through gas cromatography/mass spectrometry method for plasma sterol profile that revealed a peak corresponding to cholest-7-en-3β-ol (lathosterol).

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From lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes

et al. 2011

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Mutations of OCRL1 are associated with both the Lowe oculocerebrorenal syndrome, a multisystemic and Dent-2 disease, a renal tubulopathy. We have identified a mutation in 130 Lowe syndrome families and 6 affected by Dent-2 disease with 51 of these mutations being novel. No founding effect was evidenced for recurrent mutations. Two mutations initially reported as causing Dent-2 disease were identified in patients, including two brothers, presenting with Lowe syndrome thus extending the clinical variability of OCRL1 mutations. mRNA levels, protein content, and PiP(2) -ase activities were analyzed in patient's fibroblasts. Although mRNA levels were normal in cells harboring a missense mutation, the OCRL1 content was markedly lowered, suggesting that enzymatic deficiency resulted mainly from protein degradation rather than from a catalytic inactivation. Analysis of a splicing mutation that led to the elimination of the initiation codon evidenced the presence of shortened forms of OCRL1 that might result from the use of alternative initiation codons. The specific mapping of the frameshift and nonsense mutations, exclusively identified in exons 1-7 and exons 8-23, respectively, for Dent disease and Lowe syndrome together with the possible use of alternative initiation codons might be related to their clinical expression, that is, Lowe syndrome or Dent-2 disease.

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Klinische Befunde eines Patienten mit Lowe-Syndrom und einer Splice Site Mutation im OCRL1-Gen

Cited by 7 publications

References 15 publications

Lowe syndrome/Dent-2 disease: A comprehensive review of known and novel aspects

Lowe syndrome/Dent-2 disease: A comprehensive review of known and novel aspects

Dismetabolic Cataracts: Clinicopathologic Overview and Surgical Management with B-MICS Technique

From lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes

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