Pontocerebellar hypoplasia type 2D and optic nerve atrophy further expand the spectrum associated with selenoprotein biosynthesis deficiency

Pavlidou, Efterpi; Salpietro, Vincenzo; Phadke, Rahul; Hargreaves, Iain P.; Batten, Leigh; McElreavy, Kenneth; Pitt, Matthew; Mankad, Kshitij; Wilson, Clare; Cutrupi, Maria Concetta; Ruggieri, Martino; McCormick, David; Saggar, Anand; Kinali, Maria

doi:10.1016/j.ejpn.2015.12.016

Cited by 51 publications

(47 citation statements)

References 13 publications

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“…The English patient was diagnosed with PCH2D and optic nerve atrophy, which was not mentioned in the Iraqi patients. Elevated lactate in the English patient supports a potential involvement of mitochondria (67). According to the crystal structure, Tyr334 is located near the pyridoxal phosphate‐binding site and may affect catalytic activity (68).…”

Section: Mutations In Sepsecs Lead To Childhood Neurodegenerative Dismentioning

confidence: 88%

Why 21? The significance of selenoproteins for human health revealed by inborn errors of metabolism

Schweizer

Fradejas‐Villar

2016

FASEB j.

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Selenocysteine is the 21st proteinogenic amino acid in mammals. The human genome contains 25 genes encoding selenoproteins, and their significance for human health is increasingly recognized through the identification of patients with inborn errors in selenoprotein biosynthetic factors or in individual selenoproteins. Mutations in selenoprotein N (SEPN1) lead to a spectrum of disorders collectively called SEPN1-related myopathy, and mutations in glutathione peroxidase 4 (GPX4) cause respiratory failure and bone defects, and mutations in thioredoxin reductase 2 (TXNRD2) are associated with familial glucocorticoid deficiency. Pathogenic mutations in selenocysteine synthase (SEPSECS) cause neurodevelopmental disorders, but also other factors epistatic to selenoprotein biosynthesis, such as SECIS-binding protein 2 (SECISBP2) and tRNA, are known to cause complex disorders. Mutations in the latter 2 genes involve impaired metabolism and action of thyroid hormones, which lead to delayed bone growth and maturation. Mutations in SECISBP2 sometimes affect nervous system development, muscle, inner ear, skin, and immune system function, underlining the significance of selenoproteins for the organism. Mouse models helped to delineate the functions of selenoproteins and explain pathomechanisms. For brevity, this review is focused on human genetic disorders associated with selenoprotein deficiency and only briefly touches on health effects of nutritional selenium deficiency.-Schweizer, U., Fradejas-Villar, N. Why 21? The significance of selenoproteins for human health revealed by inborn errors of metabolism.

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Section: Mutations In Sepsecs Lead To Childhood Neurodegenerative Dismentioning

confidence: 88%

Why 21? The significance of selenoproteins for human health revealed by inborn errors of metabolism

Schweizer

Fradejas‐Villar

2016

FASEB j.

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“…PCH2D is a very rare subtype of PCH2 characterized by profound intellectual disability, progressive microcephaly, spasticity, epilepsy and progressive cerebral and cerebellar atrophy (Agamy & Zeev 2010). Additional features like axonal neuropathy, optic nerve atrophy, secondary mitochondrial dysfunction and early onset epileptic encephalopathy with burst suppression were later reported in patients with SEPSECS mutations (Anttonen et al 2015;Pavlidou et al 2016;Olson et al 2017). Disease onset was early and psychomotor development was severely delayed or absent in these patients.…”

mentioning

confidence: 78%

A SEPSECS mutation in a 23‐year‐old woman with microcephaly and progressive cerebellar ataxia

Dijk

Vermeij

Koningsbruggen

et al. 2018

J of Inher Metab Disea

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Mutations in the SEPSECS gene are associated with pontocerebellar hypoplasia type 2D. Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare autosomal recessive neurodegenerative disorders, mainly affecting pons and cerebellum. Patients have severe motor and cognitive impairments and often die during infancy. Here, we report a 23-year-old woman with slowly progressive cerebellar ataxia and cognitive impairment, in whom a homozygous missense mutation in the SEPSECS gene (c.1321G>A; p.Gly441Arg) was identified with whole exome sequencing. Our findings underline that defects in selenoprotein synthesis can also result in milder cerebellar atrophy presenting at a later age.Electronic supplementary materialThe online version of this article (10.1007/s10545-018-0151-x) contains supplementary material, which is available to authorized users.

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“…Se gives play to its biological functions basically through selenoproteins [32]. It has been reported that selenoproteins show a biological importance in the regulation of neuronal and metabolic homeostasis [33]. Our previous study found that supernutritional dietary Se did not significantly change the Se concentration in chicken brain [7].…”

Section: Discussionmentioning

confidence: 99%

Selenophosphate synthetase 1 (SPS1) is required for the development and selenium homeostasis of central nervous system in chicken (Gallus gallus)

Sun

et al. 2017

Oncotarget

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Selenophosphate synthetase (SPS) is essential for selenoprotein biosynthesis. In two SPS paralogues, SPS1 was only cloned from a cDNA library prepared from avian organ. However, the biological function of SPS1 in chicken central nervous system (CNS) remains largely unclear. To investigate the role of avian SPS1 in the development and selenium (Se) homeostasis of CNS, fertile eggs, chicken embryos, embryo neurons and chicks were employed in this study. The response of SPS1 transcription to the development and Se levels of CNS tissues was analyzed using qRT-PCR. SPS1 gene exists extensively in the development of chicken CNS. The wide expression of avian SPS1 can be controlled by the Se content levels, which suggests that SPS1 is important in the regulation of Se homeostasis. The fundamental mechanism of these effects is that Se alters the half-life and stability of SPS1 mRNA. Therefore, SPS1 exerts an irreplaceable biological function in chicken CNS and Se homeostasis is closely related to the expression of SPS1. These results suggested that SPS1 was required for the development and Se homeostasis of CNS in chicken.

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Pontocerebellar hypoplasia type 2D and optic nerve atrophy further expand the spectrum associated with selenoprotein biosynthesis deficiency

Cited by 51 publications

References 13 publications

Why 21? The significance of selenoproteins for human health revealed by inborn errors of metabolism

Why 21? The significance of selenoproteins for human health revealed by inborn errors of metabolism

A SEPSECS mutation in a 23‐year‐old woman with microcephaly and progressive cerebellar ataxia

Selenophosphate synthetase 1 (SPS1) is required for the development and selenium homeostasis of central nervous system in chicken (Gallus gallus)

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