| Texto completo | |
| Autor(es): |
Radonsky, Vanessa
;
Kizys, Marina Malta Letro
;
Dotto, Renata Pires
;
Esper, Priscila Ligeiro Goncalves
;
Heilberg, Ita Pfeferman
;
Dias-da-Silva, Magnus Regios
;
Lazaretti-Castro, Marise
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CALCIFIED TISSUE INTERNATIONAL; v. 107, n. 4, p. 6-pg., 2020-07-24. |
| 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: | 14/06570-6 - 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 |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| 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 |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| 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 |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto |