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Hypomagnesemia with Hypercalciuria Leading to Nephrocalcinosis, Amelogenesis Imperfecta, and Short Stature in a Child Carrying a Homozygous Deletion in theCLDN16Gene

Texto completo
Autor(es):
Radonsky, Vanessa [1] ; Kizys, Marina Malta Letro [1] ; Dotto, Renata Pires [1] ; Esper, Priscila Ligeiro Goncalves [2] ; Heilberg, Ita Pfeferman [2] ; Dias-da-Silva, Magnus Regios [1, 3] ; Lazaretti-Castro, Marise [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo UNIFESP, Div Endocrinol, Escola Paulista Med, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo UNIFESP, Div Nephrol, Dept Med, Escola Paulista Med, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Escola Paulista Med, Dept Med, Lab Mol & Translat Endocrinol, Div Endocrinol, Rua Pedro de Toledo 669, 11 Andar, BR-04039032 Sao Paulo, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: CALCIFIED TISSUE INTERNATIONAL; JUL 2020.
Citações Web of Science: 0
Resumo

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disease caused by mutations in theCLDN16orCLDN19gene; however, few cases develop classical amelogenesis imperfecta. Herein, we report the case of a boy with early clinical renal manifestations that started at 1 year of age and presenting with dental hypoplasia and growth delay. The patient presented with vomiting, polyuria, and polydipsia. Apart from recurrent sterile leukocyturia, erroneously treated as infectious, he was normal, except for short stature and amelogenesis imperfecta with gradually discolored teeth. Laboratory tests revealed hyperparathyroidism, hypomagnesemia, severe hypercalciuria, and hypermagnesuria on 24-h urine testing. Helical computed tomography confirmed nephrocalcinosis. We performed whole-exome sequencing (WES) to test the hypothesis of FHHNC and oligogenic inheritance of amelogenesis. Analysis of the WES binary sequence alignment/map file revealed the presence of exon 1 of theCLDN16and absence of the other exons {[}c.325\_c918{*}? (E2\_E5del)]. We confirmed aCLDN16E2\_E5 homozygous deletion by multiplex ligation-dependent probe amplification and polymerase chain reaction assays. Although most mutations causing FHHNC are missense and nonsense mutations in theCLDN16orCLDN19gene, large deletions occur and may be misled by WES, which is generally used for genetic screening of oligogenic disorders. The patient received cholecalciferol, magnesium oxide and potassium citrate. Later, the combination with hydrochlorothiazide plus amiloride was prescribed, with a good response during follow-up. Our report broadens the phenotype of FHHNC, including severe early-onset amelogenesis and short stature, and reinforces the phenotype-genotype correlation of the large deletion found inCLDN16. (AU)

Processo FAPESP: 14/15948-2 - Hipotiroidismo congênito: validação funcional in vivo do novo gene-candidato CCDC para o desenvolvimento da hemiagenesia tiroidiana
Beneficiário:Marina Malta Letro Kizys Polisel
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
Processo FAPESP: 12/01628-0 - Disgenesias tiroidianas: análise molecular e estudo funcional de mutações em genes candidatos a partir do sequenciamento de última geração numa coorte de 268 casos
Beneficiário:Marina Malta Letro Kizys Polisel
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 14/06570-6 - Sequenciamento completo do exoma, Paired-end RNA e genoma: novos insights sobre a natureza genética do câncer de tiróide na idade adulta e na faixa etária pediátrica e aplicações na prática clínica
Beneficiário:Janete Maria Cerutti
Linha de fomento: Auxílio à Pesquisa - Temático