<i>PLP1</i> gene analysis in 88 patients with leukodystrophy

Martínez‐Montero, Paloma; Muñoz-Calero, M; Vallespín, Elena; Campistol, Josep M.; Martorell, Loreto; Ruiz-Falcó, MJ; Santana, Alex Fabiano Bertollo; Pons, R; Dinopoulos, Argyrios; Sierra, Carlos Hernán; Nevado, Julián; Molano, Jesús

doi:10.1111/cge.12103

Cited by 11 publications

(5 citation statements)

References 17 publications

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“…Among these, 93 variants (85.3%) were interpreted as pathogenic or likely pathogenic (Table 1). For the X-linked recessive trait, 105 variants of 35 genes were selected from 9 reports (34)(35)(36)(37)(38)(39)(40)(41)(42). All scores are presented in Supplemental Table S3 (http://www.irdrjournal.com/action/ getSupplementalData.php?ID=113).…”

Section: Resultsmentioning

confidence: 99%

Need for revision of the ACMG/AMP guidelines for interpretation of X-linked variants

Inoue

Machida

Kita

et al. 2022

IRDR

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The guidelines provided by American College of Medical Genetics and Genomics (ACMG) and the Association of Molecular Pathology (AMP) (ACMG/AMP guidelines) suggest a framework for the classification of clinical variants. However, the interpretations can be inconsistent, with each definition sometimes proving to be ambiguous. In particular, there can be difficulty with interpretation of variants related to the X-linked recessive trait. To confirm whether there are biases in the interpretation of inherited traits, we reanalyzed variants reported prior to the release of the ACMG/AMP guidelines. As expected, the interpretation ratio as pathogenic or likely pathogenic was significantly lower for variants related to the X-linked recessive trait. Evaluation of variants related to the X-linked recessive trait, hence, need to consider whether the variant is identified only in males in accordance with the X-linked recessive trait. The ACMG/AMP guidelines should be revised to eliminate the bias revealed in this study.

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Section: Resultsmentioning

confidence: 99%

Need for revision of the ACMG/AMP guidelines for interpretation of X-linked variants

Inoue

Machida

Kita

et al. 2022

IRDR

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“…The mutations in intron3 have been showed to alter PLP1/DM20 alternative splicing, resulting in the reduced PLP1/DM20 ratio 27,32,33 . So far, a total of 36 SPG2 families have been reported worldwide, including 66 males and 16 females 8,10,18,31,34–54 . SPG2 usually starts before age 10, while adult cases have also been reported 45,48 .…”

Section: Discussionmentioning

confidence: 99%

PLP1 gene mutations cause spastic paraplegia type 2 in three families

Yao

Zhu

Zhang

et al. 2023

Ann Clin Transl Neurol

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Objective: Spastic paraplegia type 2 (SPG2) is an X-linked recessive (XLR) form of hereditary spastic paraplegia (HSP) caused by mutations in proteolipid protein 1 (PLP1) gene. We described the clinical and genetic features of three unrelated families with PLP1 mutations and reviewed PLP1-related cases worldwide to summarize the genotype-phenotype correlations. Methods: The three probands were 23, 26, and 27 years old, respectively, with progressively aggravated walking difficulty as well as lower limb spasticity. Detailed physical examination showed elevated muscle tone, hyperreflexia, and Babinski signs in lower limbs. Brain MRI examinations were investigated for all cases. PLP1 mutations were identified by whole exome sequencing, followed by Sanger sequencing, family co-segregation, and phenotypic reevaluation. Results: A total of eight patients with SPG2 were identified in these three families. The probands additionally had cognitive impairment, urinary or fecal incontinence, ataxia, and white matter lesions (WML) in periventricular regions, with or without kinetic tremor. Three hemizygous mutations in PLP1 were identified, including c.453+159G>A, c.834A>T (p.*278C), and c.434G>A (p.W145*), of which c.834A>T was first associated with HSP. Interpretation: We identified three families with complicated SPG2 due to three PLP1 mutations. Our study supports the clinically inter-and intra-family heterogeneity of SPG2. The periventricular region WML and cognitive impairment are the most common characteristics. The kinetic tremor in upper limbs was observed in 2/3 families, suggesting the spectrum of PLP1-related disorders is still expanding.

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“…The PLP1-null syndrome is a relatively mild neurology syndrome that is also graduated as a mild form of PMD, caused by other PLP1 null mutations and complete deletion of PLP1 (4,11,(15)(16)(17).…”

Section: Discussionmentioning

confidence: 99%

Dört Aileden Pelizaeus-Merzbacher Sendromlu Altı Hastanın Klinik ve Moleküler Sitogenetik Analizleri

Akkuş

Cubuk

2023

Türkiye Çocuk Hast Derg

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Objective: Pelizaeus-Merzbacher Disease is a rare X-linked recessive leukodystrophy caused by a mutation in the proteolipid protein (PLP) gene on chromosome Xq22. PMD is an early-onset neurological disorder characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay. Genetic analysis has identified Xq22 microduplications (60-70%), point mutations (10–25%), and deletions (5-10%) within the coding region of the PLP genes in Pelizaeus-Merzbacher Disease. This study evaluated six patients with PLP1 deletion and duplication in four Turkish families. Material and Methods: To detect the duplication and deletion of PLP1, chromosomal microarray analysis, and multiplex ligation-related probe amplification assays were performed. Results: In these four families, two brothers had a hemizygous deletion in the PLP1 gene, their carrier mother had a deletion in the PLP1 gene, and another two unrelated boys and one girl had duplication of the PLP1. Also, we identified the rare case of two brother patients who were found to have a hemizygous deletion in the PLP1 gene. Their carrier mother had unexplained dementia. Conclusion: Genotype-phenotype correlations of the PLP1 mutation in these families were identified in this study while trying to elucidate the genetic etiology of six individuals from four different families.

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PLP1 gene analysis in 88 patients with leukodystrophy

Cited by 11 publications

References 17 publications

Need for revision of the ACMG/AMP guidelines for interpretation of X-linked variants

Need for revision of the ACMG/AMP guidelines for interpretation of X-linked variants

PLP1 gene mutations cause spastic paraplegia type 2 in three families

Dört Aileden Pelizaeus-Merzbacher Sendromlu Altı Hastanın Klinik ve Moleküler Sitogenetik Analizleri

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