Involvement ofDFNB59 mutations in autosomal recessive nonsyndromic hearing impairment

Collin, Rob W.J.; Kalay, Ersan; Oostrik, Jaap; Çaylan, Refik; Wollnik, Bernd; Arslan, Selçuk; Hollander, Anneke I. den; Birinci, Yelda; Lichtner, Peter; Strom, Tim M.; Toraman, Bayram; Hoefsloot, Lies H.; Cremers, C.W.R.J.; Brunner, Han G.; Cremers, Frans P.M.; Karagüzel, Ahmet; Kremer, Hannie

doi:10.1002/humu.20510

Cited by 56 publications

(57 citation statements)

References 11 publications

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“…otoacoustic emissions was also observed in human patients with DFNB59 mutations [89][90][91][92] , indicating that DFNB59 mutations primarily or secondarily also affect cochlear amplification. A recent study has identified a role of pev jakin in the proliferation of peroxisomes in hair cells and SGNs in response to loud sound 93 .…”

Section: Glutamate Excitotoxicitymentioning

confidence: 85%

Auditory neuropathy — neural and synaptic mechanisms

2016

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Section: Glutamate Excitotoxicitymentioning

confidence: 85%

Auditory neuropathy — neural and synaptic mechanisms

2016

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“…Allele binning was performed with the Excel 2000 (Microsoft) macro linkage designer developed by van Camp and coworkers (37), and we checked Mendelian inheritance of alleles with PedCheck 1.0 software (http://watson.hgen.pitt.edu) (38). Multipoint LOD scores were calculated with the GeneHunter, version 2.1 release 5, program in the easyLINKAGE software package (39).…”

Section: Statisticsmentioning

confidence: 99%

Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia

Groenestege

Thebault²,

Wijst³

et al. 2007

J. Clin. Invest.

321

279

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Primary hypomagnesemia constitutes a rare heterogeneous group of disorders characterized by renal or intestinal magnesium (Mg 2+ ) wasting resulting in generally shared symptoms of Mg 2+ depletion, such as tetany and generalized convulsions, and often including associated disturbances in calcium excretion. However, most of the genes involved in the physiology of Mg 2+ handling are unknown. Through the discovery of a mutation in the EGF gene in isolated autosomal recessive renal hypomagnesemia, we have, for what we believe is the first time, identified a magnesiotropic hormone crucial for total body Mg 2+ balance. The mutation leads to impaired basolateral sorting of pro-EGF. As a consequence, the renal EGFR is inadequately stimulated, resulting in insufficient activation of the epithelial Mg 2+ channel TRPM6 (transient receptor potential cation channel, subfamily M, member 6) and thereby Mg 2+ loss. Furthermore, we show that colorectal cancer patients treated with cetuximab, an antagonist of the EGFR, develop hypomagnesemia, emphasizing the significance of EGF in maintaining Mg 2+ balance. IntroductionMagnesium (Mg 2+ ) is established as a central electrolyte in a large number of cellular metabolic reactions, including DNA synthesis, neurotransmission, and hormone receptor binding. It is a component of GTPase and a cofactor for Na,K-ATPase, adenylate cyclase, phosphoinositide kinases, and phosphofructokinase (1). Mg 2+ is also important for the regulation of parathyroid hormone release (2, 3). Accordingly, Mg 2+ deficiency (plasma Mg 2+ concentrations below 0.70 mM) has an effect on multiple body functions. Symptoms of Mg 2+ deficiency are mostly related to muscle dysfunctioning, such as tetany, prolonged QT interval, and cardiac arrhythmias (4). Children with hypomagnesemia often present with tetany and/or convulsions. Hypomagnesemia is a problem frequently observed in more than 10% of hospitalized patients and occurrences can be as high as 65% in intensive care patients (5). A long-term complication seen in many adult patients with chronic hypomagnesemia is chondrocalcinosis, which can lead to impairment of joint function (4). Mg 2+ deficiency can be secondary to systemic diseases (for instance, diabetes mellitus and Crohn disease) or to the use of osmotic agents, diuretics, and drugs such as cyclosporin and cisplatin (6). In addition, primary Mg 2+ deficiency is observed in several monogenetic disorders. Failure of early diagnosis or noncompliance with treatment can be fatal or result in permanent neurological damage.

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“…Allele binning was performed with the Excel 2000 (Microsoft) macro linkage designer developed by van Camp and coworkers (31), and we checked Mendelian inheritance of alleles with PedCheck 1.0 software (http:// watson.hgen.pitt.edu/register/docs/pedcheck.html) (32). Multipoint lod score and haplotype analysis was performed with GeneHunter, version 2.1 release 5, in the easyLINKAGE software package (33) and Haplopainter software (haplopainter.sourceforge.net/html/index.html).…”

Section: Figurementioning

confidence: 99%

A missense mutation in the Kv1.1 voltage-gated potassium channel–encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia

Glaudemans¹,

Wijst²,

Scola³

et al. 2009

J. Clin. Invest.

139

133

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Primary hypomagnesemia is a heterogeneous group of disorders characterized by renal or intestinal magnesium (Mg 2+ ) wasting, resulting in tetany, cardiac arrhythmias, and seizures. The kidney plays an essential role in maintaining blood Mg 2+ levels, with a prominent function for the Mg 2+ -transporting channel transient receptor potential cation channel, subfamily M, member 6 (TRPM6) in the distal convoluted tubule (DCT). In the DCT, Mg 2+ reabsorption is an active transport process primarily driven by the negative potential across the luminal membrane. Here, we studied a family with isolated autosomal dominant hypomagnesemia and used a positional cloning approach to identify an N255D mutation in KCNA1, a gene encoding the voltage-gated potassium (K + ) channel Kv1.1. Kv1.1 was found to be expressed in the kidney, where it colocalized with TRPM6 along the luminal membrane of the DCT. Upon overexpression in a human kidney cell line, patch clamp analysis revealed that the KCNA1 N255D mutation resulted in a nonfunctional channel, with a dominant negative effect on wild-type Kv1.1 channel function. These data suggest that Kv1.1 is a renal K + channel that establishes a favorable luminal membrane potential in DCT cells to control TRPM6-mediated Mg 2+ reabsorption.

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Involvement ofDFNB59 mutations in autosomal recessive nonsyndromic hearing impairment

Cited by 56 publications

References 11 publications

Auditory neuropathy — neural and synaptic mechanisms

Auditory neuropathy — neural and synaptic mechanisms

Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia

A missense mutation in the Kv1.1 voltage-gated potassium channel–encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia

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