First family with Perry syndrome from Mexico

Flores‑Lagunes,Leonardo; Del Pozo‑Yauner,Luis; Carrillo‑Sánchez,Karol; Molina‑Garay,Carolina; Jiménez‑Olivares,Marco; Garcia‑Solorio,Joaquin; Rodríguez Corona,Ulises; Herrera,Guillermo A.; Ricardez‑Marcial,Edgar; Alaez‑Verson,Carmen

doi:10.3892/br.2024.1808

First family with Perry syndrome from Mexico

Authors:
- Leonardo Flores‑Lagunes
- Luis Del Pozo‑Yauner
- Karol Carrillo‑Sánchez
- Carolina Molina‑Garay
- Marco Jiménez‑Olivares
- Joaquin Garcia‑Solorio
- Ulises Rodríguez Corona
- Guillermo A. Herrera
- Edgar Ricardez‑Marcial
- Carmen Alaez‑Verson
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Affiliations: Laboratory of Genomic Diagnostics, National Institute of Genomic Medicine, Mexico City 14610, Mexico, Frederick P. Whiddon College of Medicine, University of South Alabama, Mobile, Alabama 36617, USA, Montreal Clinical Research Institute Ribonucleoprotein Biochemistry Research Unit, Montréal, Quebec H2W1R7, Canada, Department of Medical Genetics, La Raza National Medical Center, Mexican Social Security Institute, Mexico City 02990, Mexico
Published online on: June 19, 2024 https://doi.org/10.3892/br.2024.1808
Article Number: 120
Copyright: © Flores‑Lagunes et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Perry syndrome (PS) is a rare autosomal dominant disease characterized by parkinsonism, central hypoventilation, weight loss and depression and is caused by pathogenic mutations in the dynactin subunit 1 (DCTN1) gene (encoding p150^glued protein). To date, only two cases have been reported in Latin America, specifically in Colombia and Argentina. The present study, to the best of our knowledge, reports the first recorded Mexican family with PS. The clinical features of the proband and a family history of early parkinsonism led to the suspicion of PS. The pathogenic variant NM_004082:c.212G>A, causing a (p.Gly71Glu) mutation in the p150^glued protein, was identified in exon 2 of the DCTN1 gene by exome sequencing, confirming the diagnosis of PS. (p.Gly71Glu) has been previously identified in at least 4 cases of PS from different ethnic backgrounds. Genetic counseling was provided to the available family members. To clarify the impact of the (p.Gly71Glu) variant on the structure and function of the cytoskeleton‑associated protein Gly rich (CAP‑Gly) domain of p150^glued, Glu71 mutated CAP‑Gly domains were modeled and compared with the wild‑type. It was hypothesized that the larger and more charged side chain of Glu may induce conformational and electrostatic changes, imposing a conformational restriction on the peptide backbone that would affect interaction with the p150^gluedprotein partners, causing dysfunction in the dynactin protein complex.

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