Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive syndrome that affects the tight junction proteins claudin-16 and claudin-19 in the thick ascending limb. In patients with claudin-19 mutations, additional symptoms such as visual impairment and other ophthalmologic findings are expected. In this report, we present a seven-year-old girl with polyuria and polydipsia. She was the daughter of consanguineous parents with a history of neonatal hypomagnesemic convulsion. On physical examination, bilateral horizontal nystagmus, retinitis pigmentosa and severe myopia were detected. Laboratory examination revealed hypomagnesemia, hypercalciuria and hypermagnesuria. A clinical diagnosis of FHHNC caused possibly by claudin-19 mutation was decided with the ocular findings. DNA analysis revealed a novel homozygous nonsense mutation (W169X) in the CLDN19 gene. In conclusion, in a patient with consanguineous parents, history of hypomagnesemic convulsion and disturbed organization and development of the retina, a diagnosis of FHHNC caused by claudin-19 mutation should be considered.
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PMID:Hypomagnesemia-hypercalciuria-nephrocalcinosis and ocular findings: a new claudin-19 mutation. 2273 4

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive tubular disorder characterized by excessive renal magnesium and calcium excretion and chronic kidney failure. This rare disease is caused by mutations in the CLDN16 and CLDN19 genes. These genes encode the tight junction proteins claudin-16 and claudin-19, respectively, which regulate the paracellular ion reabsorption in the kidney. Patients with mutations in the CLDN19 gene also present severe visual impairment. Our goals in this study were to examine the clinical characteristics of a large cohort of Spanish patients with this disorder and to identify the disease causing mutations. We included a total of 31 patients belonging to 27 unrelated families and studied renal and ocular manifestations. We then analyzed by direct DNA sequencing the coding regions of CLDN16 and CLDN19 genes in these patients. Bioinformatic tools were used to predict the consequences of mutations. Clinical evaluation showed ocular defects in 87% of patients, including mainly myopia, nystagmus and macular colobomata. Twenty two percent of patients underwent renal transplantation and impaired renal function was observed in another 61% of patients. Results of the genetic analysis revealed CLDN19 mutations in all patients confirming the clinical diagnosis. The majority of patients exhibited the previously described p.G20D mutation. Haplotype analysis using three microsatellite markers showed a founder effect for this recurrent mutation in our cohort. We also identified four new pathogenic mutations in CLDN19, p.G122R, p.I41T, p.G75C and p.G75S. A strategy based on microsequencing was designed to facilitate the genetic diagnosis of this disease. Our data indicate that patients with CLDN19 mutations have a high risk of progression to chronic renal disease.
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PMID:Claudin-19 mutations and clinical phenotype in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. 2330 Oct 36

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disorder caused by mutations in the CLDN16 or CLDN19 genes, encoding claudin-16 and claudin-19 in the thick ascending limb of Henle's loop. In patients with claudin-19 mutations, severe ocular involvement (macular coloboma, pigmentary retinitis, nystagmus, or visual loss) has been described. In this report, we presented a 12-year-old girl with rickets, polyuria, and polydipsia. She was the daughter of consanguineous parents, and she had a history of recurred hypocalcemic and hypomagnesemic tetany. On physical examination, bilateral horizontal nystagmus and severe myopia were detected. Laboratory examination revealed hypomagnesemia, hypocalcemia, hypercalciuria, nephrocalcinosis, and renal stone. A clinical diagnosis of FHHNC caused possibly by claudin-19 mutation was decided with the ocular findings. DNA analysis revealed a novel homozygous missense mutation c.241C>T in the CLDN19 gene. In conclusion, in a patient with hypomagnesemia, hypercalciuria, nephrocalcinosis, and ocular findings, a diagnosis of FHHNC caused by claudin-19 mutation should be considered. This is the first study of FHHNC in Chinese population. Our findings of the novel mutation c.241C>T in exon 2 add to the list of more than 16 mutations of CLDN19 gene reported.
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PMID:First report of a novel missense CLDN19 mutations causing familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a Chinese family. 2555 44

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal-recessive renal tubular disorder characterized by excessive urinary losses of magnesium and calcium, bilateral nephrocalcinosis and progressive chronic renal failure. Presentation with FHHNC symptoms generally occurs early in childhood or before adolescence. At present, the only therapeutic option is supportive and consists of oral magnesium supplementation and thiazide diuretics. However, neither treatment seems to have a significant effect on the levels of serum magnesium or urine calcium or on the decline of renal function. In end-stage renal disease patients, renal transplantation is the only effective approach. This rare disease is caused by mutations in the CLDN16 or CLDN19 genes. Patients with mutations in CLDN19 also present severe ocular abnormalities such as myopia, nystagmus and macular colobamata. CLDN16 and CLDN19 encode the tight-junction proteins claudin-16 and claudin-19, respectively, which are expressed in the thick ascending limb of Henle's loop and form an essential complex for the paracellular reabsorption of magnesium and calcium. Claudin-19 is also expressed in retinal epithelium and peripheral neurons. Research studies using mouse and cell models have generated significant advances on the understanding of the pathophysiology of FHHNC. A recent finding has established that another member of the claudin family, claudin-14, plays a key regulatory role in paracellular cation reabsorption by inhibiting the claudin-16-claudin-19 complex. Furthermore, several studies on the molecular and cellular consequences of disease-causing CLDN16 and CLDN19 mutations have provided critical information for the development of potential therapeutic strategies.
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PMID:Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis: clinical and molecular characteristics. 2661 20

Michaelis-Manz syndrome is an autosomal recessive hereditary tubulopathy associated with mutations in the tight-junction proteins claudin-16 and claudin-19, which are present in the distal convoluted tubule and the loop of Henle in the kidney. Claudin-19 is also expressed in the retinal pigmentary epithelium. The clinical picture causes hypomagnesemia, hyper-calciuria and nephrocalcinosis that can lead to renal failure, which is the condition that marks the prognosis of the disease. Ophthalmologically patients can present macular coloboma, myopic staphyloma and nystagmus. We present the case report of an 18-year-old man suffering from hereditary hypomagnesemia, hypercalciuria and nephrocalcinosis, or Mich-aelis-Manz syndrome, with macular coloboma and stable visual acuities. Keywords. Hypomagnesemia. Hypercalciuria. Nephrocalcinosis. Macular coloboma.
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PMID:[Michaelis-Manz syndrome. A case report]. 3042 85