A novel CLDN16 mutation in a large family with familial hypomagnesaemia with hypercalciuria and nephrocalcinosis

BMC Research Notes

John A Sayer²  Simon HS Pearce²  Hormazdiar Dastoor³  Job Simon¹  Salima Atia Abood¹  Asma Deeb¹ 

[1] Endocrinology Department, Mafraq Hospital, AbuDhabi, United Arab Emirates;Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK;Nephrology Department, Mafraq Hospital, AbuDhabi, United Arab Emirates

关键词: End stage renal disease;    Nephrocalcinosis;    Hypomagnesaemia;    Hypocalcaemia;    Hypercalciuria;    Claudin-16;    CLDN16;   

Others  :  1140500
DOI  :  10.1186/1756-0500-6-527

 received in 2013-03-26, accepted in 2013-12-05,  发布年份 2013

【 摘 要 】

Background

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is a rare tubulopathy leading to renal calcification and progressive renal failure.

Case presentation

We report a consanguineous Arab family (of Qatari origin) with 7 affected siblings with variable phenotypes including hypomagnesaemia, hypercalciuria, nephrocalcinosis and renal stones. Presenting features included haematuria and recurrent urinary tract infections. As the biochemical and clinical phenotypes of this family resembled familial hypomagnesaemia with hypercalciuria and nephrocalcinosis, we performed genetic investigation in order to provide a precise molecular diagnosis. We screened all coding regions of the CLDN16 gene and identified a novel mutation (c.G647A, p.R216H) which was found homozygously in the six severely affected cases, who manifested significant nephrocalcinosis, often nephrolithiasis and sometimes reduced GFR. Parents were both heterozygous for the mutation and, together with children carrying the mutation in its heterozygous state, exhibited mild or no biochemical phenotypes.

Conclusion

Mutations in CLDN16 underlie familial hypomagnesaemia with hypercalciuria and nephrocalcinosis but remain a rare cause of nephrocalcinosis and nephrolithiasis. Management includes reduction of hypercalciuria with thiazide diuretics, correction of serum magnesium and close monitoring of renal function given the significant risk of end stage renal failure with this inherited form of nephrocalcinosis.

【 授权许可】

   
2013 Deeb et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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