PNPLA6 disorders: what's in a name?

被引:3
作者
Liu, James [1 ]
Hufnagel, Robert B. [1 ,2 ]
机构
[1] NEI, NIH, Ophthalm Genet & Visual Funct Branch, Bethesda, MD USA
[2] NEI, NIH, Ophthalm Genet & Visual Funct Branch, Bldg 10,Room 10N109,MSC1860 10 Ctr Dr, Bethesda, MD 20892 USA
关键词
PNPLA6; NTE; Spastic paraplegia type 39; Gordon-Holmes syndrome; Boucher-Neuhauser syndrome; Laurence-Moon syndrome; Oliver-McFarlane syndrome; NEUROPATHY TARGET ESTERASE; MOTOR-NEURON DISEASE; NEUROTOXIC-ESTERASE; BOUCHER-NEUHAUSER; CATALYTIC DOMAIN; ORGANOPHOSPHORUS COMPOUNDS; SUBCELLULAR-DISTRIBUTION; PHOSPHORYLATION SITE; BRAIN; MUTATIONS;
D O I
10.1080/13816810.2023.2254830
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Variants in the patatin-like phospholipase domain containing 6 (PNPLA6) gene cause a broad spectrum of neurological disorders characterized by gait disturbance, visual impairment, anterior hypopituitarism, and hair anomalies. This review examines the clinical, cellular, and biochemical features found across the five PNPLA6-related diseases, with a focus on future questions to be addressed.Materials and Methods: A literature review was performed on published clinical reports on patients with PNPLA6 variants. Additionally, in vitro and in vivo models used to study the encoded protein, Neuropathy Target Esterase (NTE), are summarized to lend mechanistic perspective to human diseases.Results: Biallelic pathogenic PNPLA6 variants cause five systemic neurological disorders: spastic paraplegia type 39, Gordon-Holmes, Boucher-Neuhauser, Laurence-Moon, and Oliver-McFarlane syndromes. PNPLA6 encodes NTE, an enzyme involved in maintaining phospholipid homeostasis and trafficking in the nervous system. Retinal disease presents with a unique chorioretinal dystrophy that is phenotypically similar to choroideremia and Leber congenital amaurosis. Animal and cellular models support a loss-of-function mechanism.Conclusions: Clinicians should be aware of choroideremia-like ocular presentation in patients who also experience growth defects, motor dysfunction, and/or hair anomalies. Although NTE biochemistry is well characterized, further research on the relationship between genotype and the presence or absence of retinopathy should be explored to improve diagnosis and prognosis.
引用
收藏
页码:530 / 538
页数:9
相关论文
共 69 条
[41]  
Lush MJ, 1998, BIOCHEM J, V332, P1
[42]   PROGRESSIVE DEFICIT OF RETROGRADE AXONAL-TRANSPORT IS ASSOCIATED WITH THE PATHOGENESIS OF DI-N-BUTYL DICHLORVOS AXONOPATHY [J].
MORETTO, A ;
LOTTI, M ;
SABRI, MI ;
SPENCER, PS .
JOURNAL OF NEUROCHEMISTRY, 1987, 49 (05) :1515-1522
[43]   Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice [J].
Moser, M ;
Li, Y ;
Vaupel, K ;
Kretzschmar, D ;
Kluge, R ;
Glynn, P ;
Buettner, R .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (04) :1667-1679
[44]   Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila [J].
Mühlig-Versen, M ;
da Cruz, AB ;
Tschäpe, JA ;
Moser, M ;
Büttner, R ;
Athenstaedt, K ;
Glynn, P ;
Kretzschmar, D .
JOURNAL OF NEUROSCIENCE, 2005, 25 (11) :2865-2873
[45]   Organophosphorus Nerve Agents: Types, Toxicity, and Treatments [J].
Mukherjee, Sudisha ;
Gupta, Rinkoo Devi .
JOURNAL OF TOXICOLOGY, 2020, 2020
[46]   Multifaceted and Age-Dependent Phenotypes Associated With Biallelic PNPLA6 Gene Variants: Eight Novel Cases and Review of the Literature [J].
Nanetti, Lorenzo ;
Di Bella, Daniela ;
Magri, Stefania ;
Fichera, Mario ;
Sarto, Elisa ;
Castaldo, Anna ;
Mongelli, Alessia ;
Baratta, Silvia ;
Fenu, Silvia ;
Moscatelli, Marco ;
Bonati, Maria Teresa ;
Martinuzzi, Andrea ;
Mariotti, Caterina ;
Taroni, Franco .
FRONTIERS IN NEUROLOGY, 2022, 12
[47]  
National Center for Biotechnology Information (NCBI), National center for biotechnology information (NCBI)
[48]  
Parascandola J, 1994, Pharm Hist, V36, P123
[49]   A new PNPLA6 mutation presenting as Oliver McFarlane syndrome [J].
Patsi, O. ;
De Beaufort, C. ;
Kerschen, P. ;
Cardillo, S. ;
Soehn, A. ;
Rautenberg, M. ;
Diederich, N. J. .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2018, 392 :1-2
[50]   Evidence that mouse brain neuropathy target esterase is a lysophospholipase [J].
Quistad, GB ;
Barlow, C ;
Winrow, CJ ;
Sparks, SE ;
Casida, JE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (13) :7983-7987