@entity1272 with secondary @entity3747 is a rare @entity74 characterized by profound @entity1272 associated with @entity3747 . Pathophysiology is related to impaired intestinal absorption of @entity1760 accompanied by renal @entity1760 wasting as a result of a reabsorption defect in the distal convoluted tubule. Recently, mutations in the @entity31566 gene coding for @entity31566 , a member of the transient receptor potential (TRP) family of cation channels, were identified as the underlying @entity74 . Here, the results of a @entity31566 mutational analysis of 21 families with 28 affected individuals are presented. In this large @entity1 cohort, a retrospective clinical evaluation based on a standardized questionnaire was also performed. Genotype analysis revealed @entity31566 mutations in 37 of 42 expected mutant alleles. Sixteen new @entity31566 mutations were identified, including stop mutations, frame-shift mutations, splice-site mutations, and deletions of exons. Electrophysiologic analysis of mutated ion channels after heterologous expression in @entity1238 oocytes proved complete loss of function of @entity31566 . Clinical evaluation revealed a homogeneous clinical picture at manifestation with onset in early infancy with generalized cerebral convulsions. Initial laboratory evaluation yielded extremely low serum @entity1760 levels, low serum @entity460 levels, and inadequately low parathyroid hormone levels. Treatment usually consisted of acute intravenous @entity1760 supplementation leading to relief of clinical symptoms and normocalcemia, followed by lifelong oral @entity1760 supplementation. Serum @entity1760 levels remained in the subnormal range despite adequate therapy. This is best explained by a disturbed @entity1760 conservation in the distal convoluted tubule, which emerged in all @entity1 upon @entity1760 supplementation. Delay of diagnosis resulted in permanent @entity16 in three @entity1 .

Novel XXXX mutations in 21 families with @entity1272 and secondary @entity3747 .

@entity3747 :: ('MESH:D006996', 'Disease') :: ['hypocalcemia'] @entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity1238 :: ('8355', 'Species') :: ['Xenopus'] @entity31566 :: ('140803', 'Gene') :: ['TRPM6'] @entity1272 :: ('MESH:C537153', 'Disease') :: ['Primary hypomagnesemia', 'hypomagnesemia'] @entity16 :: ('MESH:D009422', 'Disease') :: ['neurologic damage'] @entity74 :: ('MESH:D030342', 'Disease') :: ['genetic defect', 'autosomal recessive disorder'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity1760 :: ('MESH:D008274', 'Chemical') :: ['magnesium']
@entity31566 :: (140803,Gene) :: ['TRPM6']
