Endocrine · 2021
Kidney malformations and Hirschsprung's disease in carriers of cysteine mutations in exon 10 of the RET proto-oncogene.
СтатьяНазвание и аннотация: Перевод в очереди
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Machens Andreas, Lorenz Kerstin, Dralle Henning
Аннотация
PURPOSE: This investigation aimed at characterizing penetrance and interrelation of the loss-of-function phenotypes, Hirschsprung's disease and kidney malformations, in carriers of exon 10 REarranged during Transfection (RET) mutations.
METHODS: Comparative analysis of penetrance of and interdependencies between Hirschsprung's disease and kidney malformations among carriers of mutations in RET codons 609, 611, 618, and 620.
RESULTS: Hirschsprung's disease and kidney malformations (kidney agenesis, ureteropelvicalyceal dilatation, or polycystic kidney disease) each affected 3.6% (4 patients) of 112 carriers of RET mutations in exon 10. This percentage increased to 13% (4 patients) and 9% (3 patients) of 32 p.Cys620 carriers and 22% (4 patients) and 17% (3 patients) of 18 p.Cys620Arg carriers, respectively. Overall, Hirschsprung's disease (17%, 4 of 24 carriers; P = 0.002) and kidney malformations (13%, 3 of 24 carriers; P = 0.030) were associated with arginine-for-cysteine substitutions. Two of the six patients, originating from different p.Cys620Arg families, harbored both Hirschsprung's disease and kidney malformations.
CONCLUSION: Hirschsprung's disease and kidney malformations are the more penetrant, the closer the cysteine mutations are located to the transmembrane domain (codon 636-657) of the RET kinase receptor.
METHODS: Comparative analysis of penetrance of and interdependencies between Hirschsprung's disease and kidney malformations among carriers of mutations in RET codons 609, 611, 618, and 620.
RESULTS: Hirschsprung's disease and kidney malformations (kidney agenesis, ureteropelvicalyceal dilatation, or polycystic kidney disease) each affected 3.6% (4 patients) of 112 carriers of RET mutations in exon 10. This percentage increased to 13% (4 patients) and 9% (3 patients) of 32 p.Cys620 carriers and 22% (4 patients) and 17% (3 patients) of 18 p.Cys620Arg carriers, respectively. Overall, Hirschsprung's disease (17%, 4 of 24 carriers; P = 0.002) and kidney malformations (13%, 3 of 24 carriers; P = 0.030) were associated with arginine-for-cysteine substitutions. Two of the six patients, originating from different p.Cys620Arg families, harbored both Hirschsprung's disease and kidney malformations.
CONCLUSION: Hirschsprung's disease and kidney malformations are the more penetrant, the closer the cysteine mutations are located to the transmembrane domain (codon 636-657) of the RET kinase receptor.