Mutations in PMM2 gene in four unrelated Spanish families with polycystic kidney disease and hyperinsulinemic hypoglycemia.

Fecha de publicación: 25/08/2020 Fecha Ahead of Print: 25/08/2020

Autores de IIS La Fe

Francisca Moreno Macián

Autor
Maria Carmen De Mingo Alemany

Autor
Sara León Cariñena

Autor
Pedro Ortega Lopez

Autor
Dolores Rausell Felix

Autor
Maria Jose Aparisi Navarro

Autor
Marina Martinez Matilla

Autor
Cristina Cardona Gay

Autor
Francisco Martínez Castellano

Autor
Vicente Jose Albiach Mesado

Autor

Grupos

Investigación Traslacional en Genética

Leader

Francisco Martínez Castellano

Abstract

Objectives Hyperinsulinemic hypoglucemia (HH) is characterized by a dysregulation of insulin secretion from pancreatic ß cells. Congenital hyperinsulinism has been associated with specific genes in monogenic forms and also with other diseases with a yet unknown genetic cause. In 2017, Rubio Cabezas et al. described the association of HH and autosomal recessive polycystic kidney disease (ARPKD) with a promoter mutation in the PMM2 gene. They found that all the patients carried a promoter mutation (c-167G>T) in PMM2, either homozygous or in trans with a second PMM2 coding mutation. Methods We performed the study of the PMM2 gene in six patients from four unrelated families, previously diagnosed with ARPKD and HH. Results All these patients had in common the heterozygous variant c-167G>T in the promoter region for PMM2. Additionally, each patient carried a compound heterozygote for a second missense mutation in this gene (p.Arg141His, p.Asp148Asn or p.Phe157Ser), previously reported as pathogenic for congenital disorder of glycosylation type Ia, with an autosomal recessive inheritance pattern. Unlike the previous published article, two of our patients showed altered type 1 pattern and one of them with rectal bleeding that could be a sign of PMM2-congenital disorders of glycosylation. Conclusion We propose the study of this gene when carrying out the diagnosis of patients with HH, especially in the neonatal period and when a recessive polycystic kidney disease without alterations in PKDH1 is diagnosed.

Datos de la publicación

ISSN/ISSNe:: 0334-018X, 2191-0251
Tipo:: Article
Páginas:: 1283-1288
DOI:: 10.1515/jpem-2020-0168
Factor de Impacto:: 0,502 SCImago ℠
Cuartil:: Q2 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

Moreno Macián F:: Pediatric Endocrinology, Hospital Universitari i Politecnic La Fe, Valencia, Spain
De Mingo Alemany C:: Pediatric Endocrinology, Hospital Universitari i Politecnic La Fe, Valencia, Spain
León Cariñena S:: Pediatric Endocrinology, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Ortega López P:: Pediatric Nephrology, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Rausell Felix D:: Metabolopathies Unit, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Aparisi Navarro M:: Instituto de Investigación. Genomic Unit Health Research Institute, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Martinez Matilla M:: Instituto de Investigación. Genomic Unit Health Research Institute, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Cardona Gay C:: Instituto de Investigación. Genomic Unit Health Research Institute, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Martinez Castellano F:: Instituto de Investigación. Genomic Unit Health Research Institute, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Albiach Mesado V:: Pediatric Endocrinology, Hospital Universitari i Politecnic La Fe, Valencia, Spain