TSC2/PKD1 contiguous gene syndrome, with emphasis on a case with an atypical mild polycystic kidney phenotype and a novel genetic variant
Por:
Reyna-Fabian, Miriam E., Alcantara-Ortigoza, Miguel A., Hernandez-Martinez, Nancy L., Berumen, Jaime, Jimenez-Garcia, Raquel, Gomez-Garza, Gilberto, Gonzalez-del Angel, Ariadna
Publicada:
1 ene 2020
Categoría:
Nephrology
Resumen:
About 80% of patients with tuberous sclerosis complex (TSC) present
renal involvement, usually as angiomyolipomas followed by cystic
disease. An early diagnosis of polycystic kidney disease (PKD) in such
patients is frequently related to the TSC2/PKD1 contiguous gene syndrome
(PKDTS). Molecular confirmation of PKDTS is important for a prompt
diagnosis, which can be complicated by the phenotypic heterogeneity of
PKD and the absence of a clear phenotypegenotype correlation. Herein, we
report three PKDTS pediatric patients. The case 3 did not present a
classic PKDTS phenotype, having only one observable cyst on renal
ultrasound at age 4 and multiple small cysts on magnetic resonance
imaging at age 15. In this patient, chromosomal microarray analysis
showed a gross deletion of 230.8 kb that involved TSC2, PKD1 and 13
other protein-coding genes, plus a heterozygous duplication of a
previously undescribed copy number variant of 242.9 kb that involved six
protein-coding genes, including SSTR5, in the 16p13.3 region. Given the
observations that the case 3 presented the mildest renal phenotype,
harbored three copies of SSTR5, and the reported inhibition of
cystogenesis (specially in liver) observed with somatostatin analogs in
some patients with autosomal dominant PKD, it can be hypothesized that
other genetic factors as the gene dosage of SSTR5 may influence the PKD
phenotype and the progression of the disease; however, future work is
needed to examine this possibility. (C) 2019 Sociedad Espanola de
Nefrologia. Published by Elsevier Espana, S.L.U.
Filiaciones:
Reyna-Fabian, Miriam E.:
Secretaria Salud Mexico, Inst Nacl Pediat, Dept Genet Humana, Lab Biol Mol, Insurgentes Sur 3700-C, Mexico City 04530, DF, Mexico
Alcantara-Ortigoza, Miguel A.:
Secretaria Salud Mexico, Inst Nacl Pediat, Dept Genet Humana, Lab Biol Mol, Insurgentes Sur 3700-C, Mexico City 04530, DF, Mexico
Hernandez-Martinez, Nancy L.:
Secretaria Salud Mexico, Inst Nacl Pediat, Dept Genet Humana, Lab Biol Mol, Insurgentes Sur 3700-C, Mexico City 04530, DF, Mexico
Berumen, Jaime:
Univ Nacl Autonoma Mexico, Fac Med, Dept Med Expt, Mexico City, DF, Mexico
Hosp Gen Mexico City, Unidad Med Genom, Mexico City, DF, Mexico
Jimenez-Garcia, Raquel:
Secretaria Salud Mexico, Inst Nacl Pediat, Serv Nefrol, Mexico City, DF, Mexico
Gomez-Garza, Gilberto:
Secretaria Salud Mexico, Inst Nacl Ped, Resonancia Magnet, Mexico City, DF, Mexico
Gonzalez-del Angel, Ariadna:
Secretaria Salud Mexico, Inst Nacl Pediat, Dept Genet Humana, Lab Biol Mol, Insurgentes Sur 3700-C, Mexico City 04530, DF, Mexico
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