A rare mutation in the EPG5 gene causes Vici syndrome

Demiral, Emine; Şen, Aşkın; Esener, Z.; Ceylaner, Serdar; Tekedereli, İbrahim

doi:10.1097/mcd.0000000000000233

Cited by 3 publications

(4 citation statements)

References 11 publications

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“…In addition to these phenotypic features, cardiomyopathy, developmental delay, microcephaly, and failure to thrive were described as typical consequences (Byrne et al., ; Chiyonobu et al., ; del Campo et al., ). Since the first description, more than 40 families have been published with Vici syndrome (VICIS), who were compatible with an autosomal recessive transmission and have extended the variable clinical spectrum with myopathy, epilepsy, elevated aminotransferases, thymus aplasia, thrombocytopenic purpura, sensorineural hearing loss, and renal tubular acidosis (Aggarwal, Tandon, Bhowmik, & Dalal, ; Al‐Owain et al., ; Alzahrani, Alghamdi, & Waggass, ; Balasubramaniam et al., ; Byrne et al., ; Chiyonobu et al., ; Cullup et al., ; del Campo et al., ; Demiral, Sen, Esener, Ceylaner, & Tekedereli, ; El‐Kersh, Jungbluth, Gringras, & Senthilvel, ; Hedberg‐Oldfors, Darin, & Oldfors, ; Hori et al., ; Huenerberg et al., ; Maillard et al., ; McClelland et al., ; Miyata et al., ; Ozkale, Erol, Gümüs, Ozkale, & Alehan, ; Rogers, Aufmuth, & Monesson, ; Said, Soler, & Sewry, ; Shimada et al., ; Waldrop et al., ). The prognosis was found to be poor with a median survival of 42 months (Byrne, Dionisi‐Vici, Smith, Gautel, & Jungbluth, ).…”

Section: Introductionmentioning

confidence: 99%

EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome

Vojcek

Keszthelyi

Jávorszky

et al. 2019

Annals of Human Genetics

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We report on a sibling pair with the EPG5 c.1007A > G mutation who developed a severe form of Vici syndrome and died in infancy. The c.1007A > G (p.Gln336Arg) mutation, affecting the penultimate nucleotide and the splicing of exon 2 is the most common mutation of EPG5 and is typically associated with a less devastating prognosis: cardiomyopathy and cataract are less frequent consequences and the median survival time is 78 months compared to an overall median survival of 42 months. The less severe course related to c.1007A > G was formerly explained by the preserved canonical splicing in 25% of the transcripts. In contrast, we found the messenger RNA encoded by the c.1007A > G allele to be absent, explaining the severe course of the disease. This family provides another example of phenotypic variability related to a differential splicing. K E Y W O R D Sdifferential splicing, Gln336Arg, phenotype variability, Vici syndrome 80 wileyonlinelibrary.com/journal/ahg Ann Hum Genet. 2020;84:80-86.

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Section: Introductionmentioning

confidence: 99%

EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome

Vojcek

Keszthelyi

Jávorszky

et al. 2019

Annals of Human Genetics

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“…However, the extent to which the immune system is compromised differs from person to person, with some patients harbouring almost normal immunity (Finocchi et al, 2012). The affected individuals may develop certain less frequent clinical presentations such as seizures, renal tubular acidosis, cleft lip and palate, laryngomalacia, idiopathic thrombocytopenic purpura, thymic aplasia and sensorineural hearing loss (Demiral et al, 2018;Huenerberg et al, 2016;McClelland et al, 2010;Miyata et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…In 2018, Alzahrani and his colleges described a Saudi male infant affected by VICIS and died at the age of 8 months (Alzahrani et al, 2018). In the same year, Demiral et al reported a Turkish male patient died of VICIS due to sepsis at 1 year and 9 months old (Demiral et al, 2018). Nevertheless, Byrne, Jansen, et al (2016) concluded that approximately 10% of the VICIS patients could survive until the age of 5 and observed simultaneously that one patient was still alive at 10 years old.…”

Section: Discussionmentioning

confidence: 99%

The first Chinese case of Vici syndrome with novel compound heterozygous sequence variants in EPG5

Dong

Zhang

et al. 2021

Intl J of Devlp Neuroscience

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Background: Vici syndrome (VICIS) refers to a clinical spectrum of multiple organ systems characterized by corpus callosum agenesis, hypopigmentation, cataracts, cardiomyopathy and immunodeficiency. The aims of this study were to describe detailed clinical and molecular features of two Chinese female siblings and to review several previous findings. Methods: Targeted sequencing panel involving all known disease-causing genes of monogenic disorders combined with Sanger sequencing validation were performed to identify the likely pathogenic sequence variants of the proband with VICIS.Results: The proband diagnosed as VICIS presented with neonatal pneumonia, myocardial damage, hypotonia, maxillofacial malformations, hearing impairment, failure to thrive and died 40 days after birth. Two novel missense variants in ectopic P-granules autophagy protein 5 homologue (EPG5, NM_020964.3) were identified in this proband. The two likely pathogenic variants c.1609G > A (p.(E537K)) and c.5764C>G (p.(P1922A)) were assessed as damaging by bioinformatic analysis. As these variants were absent in 150 unrelated Chinese normal controls and inherited from asymptomatic parents in the co-segregation analysis, the compound heterozygous EPG5 variants were responsible for the clinical features of this patient. Finally, she was genetically diagnosed with VICIS.Conclusions: To our knowledge, this is the first Chinese case of VICIS. Our report identified novel compound heterozygous EPG5 sequence variants in the proband with VICIS, highlighting the rarity and high mortality rate of VICIS and emphasizing on the importance of high-throughput sequencing in confirmed diagnosis of monogenic diseases, which could further facilitate the development of genetic counselling and prenatal diagnosis.

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“…To date (updated Oct 2021), 56 different mutations have been described throughout the entire EPG5 coding sequence, but clear genotype-phenotype correlations have not been established [4,[6][7][8]. Most mutations are unique to individuals or families, with only five recurrent mutations reported [7,9,10].…”

Section: Introductionmentioning

confidence: 99%

Phenotypic expansion of EGP5-related Vici syndrome: 15 Dutch patients carrying a founder variant

Vansenne

Fock²,

Stolte‐Dijkstra³

et al. 2022

European Journal of Paediatric Neurology

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A rare mutation in the EPG5 gene causes Vici syndrome

Cited by 3 publications

References 11 publications

EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome

EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome

The first Chinese case of Vici syndrome with novel compound heterozygous sequence variants in EPG5

Phenotypic expansion of EGP5-related Vici syndrome: 15 Dutch patients carrying a founder variant

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