Prenatal diagnosis of familial recessive PIGN mutation associated with multiple anomalies: A case report

Sun, Limei; Yang, Xiao-Ning; Xu, Yasong; Sun, Shiyu; Wu, Qichang

doi:10.1016/j.tjog.2021.03.026

Cited by 7 publications

(9 citation statements)

References 15 publications

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“…One example is the synonymous c.963G>A; p.Gln321Gln variant, predicted to affect splicing 9 . This variant has been reported in six reports describing patients of Asian ancestry with PIGN encephalopathy 9,14,17,18,22,24 and is also present in 18 East Asian genomes in gnomAD. Another example is the recurrent p.Leu311Trp pathogenic variant, which we identified in 10 unrelated patients of European ancestry in our cohort.…”

Section: Discussionmentioning

confidence: 98%

“…Although 65% (28/43) of patients with PIGN diseases have epilepsy, 8–21,23,24 the reports of 11 of 28 patients simply refer to seizures 10,12–14,16,19,21 . For the remaining cases, limited data regarding the epileptology are provided.…”

Section: Introductionmentioning

confidence: 99%

“…A genotype-phenotype correlation of biallelic loss-of-function variants associated with the severe phenotypes (multiple congenital anomalies and Fryns syndrome) has been suggested. 8,16 Although 65% (28/43) of patients with PIGN diseases have epilepsy, [8][9][10][11][12][13][14][15][16][17][18][19][20][21]23,24 the reports of 11 of 28 patients simply refer to seizures. 10,[12][13][14]16,19,21 For the remaining cases, limited data regarding the epileptology are provided.…”

Section: Introductionmentioning

confidence: 99%

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PIGNencephalopathy: Characterizing the epileptology

et al. 2022

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proteins include enzymes, adhesion molecules, receptors, and regulatory proteins of the immune system. 4 Recently, PIGN has been shown to also mediate protein quality control within ER, contributing to maintaining chromosomal stability. 5,6 Biallelic disease-causing variants in genes involved in the GPI synthesis pathway have been associated with epilepsy, developmental delay (DD), intellectual disability (ID), hypotonia, and multiple congenital anomalies affecting different organs. 2,7 Forty-three patients with PIGN diseases from 32 families with 42 unique PIGN variants, including 10

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PIGNencephalopathy: Characterizing the epileptology

et al. 2022

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“…Biallelic PIGN variants often cause various clinical manifestations, including visceral abnormalities or dysmorphic features (> 90%), psychomotor development delay (100%), hypotonia (100%), and seizures (93%) [ 3 , 8 ]. Such variants may even be lethal in the fetal or neonatal period, and can lead to multiple congenital anomalies-hypotonia-seizures syndrome and Fryns syndrome [ 2 , 9 ]. However, many cases cannot be classified as either of the syndromes, as the genotype–phenotype associations of PIGN are not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Damaging novel mutations in PIGN cause developmental epileptic-dyskinetic encephalopathy: a case report

Tian

Chen

et al. 2022

BMC Pediatr

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Background Mutations in PIGN, resulting in a glycosylphosphatidylinositol (GPI) anchor deficiency, typically leads to multiple congenital anomalies-hypotonia-seizures syndrome. However, the link between PIGN and epilepsy or paroxysmal non-kinesigenic dyskinesia (PNKD) is not well-described. This study reported a patient with PIGN mutation leading to developmental and epileptic encephalopathy and PNKD, to expand upon the genotype–phenotype correlation of PIGN. Case presentation During the first 10 days of life, a girl exhibited paroxysmal staring episodes with durations that ranged from several minutes to hours. These episodes occurred 2–5 times daily and always occurred during wakefulness. Ictal electroencephalography revealed no abnormalities, and PNKD was diagnosed. The patient also exhibited severely delayed psychomotor development and generalized seizures at the age of 4 months. Results of brain magnetic resonance imaging and metabolic screenings were normal, but trio-based whole-exome sequencing identified two novel compound heterozygous PIGN mutations (NM_176787; c.163C > T [p.R55 > X] and c.283C > T [p.R95W]). Flow cytometry analysis of the patient’s granulocytes revealed dramatically reduced expression of GPI-anchored proteins. This indicated that the mutations compromised GPI functions. The patient got seizure-free for 1 year, and her dyskinesia episodes reduced significantly (1–2 times/month) after treatment with levetiracetam (600 mg/day) and clonazepam (1.5 mg/day). No progress was observed with respect to psychomotor development; however, no craniofacial dysmorphic features, cleft lip/palate, brachytelephalangy with nail hypoplasia, and internal malformations have been observed until now (6 years of age). Conclusion This is the first study to document developmental and epileptic encephalopathy with PNKD in a human with PIGN mutations. This report expanded our understanding of the genotype–phenotype correlation of PIGN, and PIGN may be considered a potentially relevant gene when investigating cases of epilepsy or PNKD.

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“…The mean time of the first seizure was 6.9 months. Mutation in PIGN gene were found in two fetuses, who developed cystic hygroma and other malformations, such as tetralogy of Fallot (24,38,(49)(50)(51)(52)(53).…”

Section: Pign (Phosphatidylinositol Glycan Anchor Biosynthesis Class N Protein; Mim 606097)mentioning

confidence: 99%

Spectrum of Neurological Symptoms in Glycosylphosphatidylinositol Biosynthesis Defects: Systematic Review

et al. 2022

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Background: Mutations of genes involved in the synthesis of glycosylphosphatidylinositol and glycosylphosphatidylinositol-anchored proteins lead to rare syndromes called glycosylphosphatidylinositol-anchored proteins biosynthesis defects. Alterations of their structure and function in these disorders impair often fundamental processes in cells, resulting in severe clinical image. This study aimed to provide a systematic review of GPIBD cases reports published in English-language literature.Methods: The browsing of open-access databases (PubMed, PubMed Central. and Medline) was conducted, followed by statistical analysis of gathered information concerning neurological symptomatology. The inclusion criteria were: studies on humans, age at onset (<18 y.o.), and report of GPIBD cases with adequate data on the genetic background and symptomatology. Exclusion criteria were: publication type (manuscripts, personal communication, review articles); reports of cases of GPI biosynthesis genes mutations in terms of other disorders; reports of GPIBD cases concentrating on non-neurological symptoms; or articles concentrating solely on the genetic issues of GPI biosynthesis. Risk of bias was assessed using Joanna Brigs Institute Critical Appraisal Checklists. Data synthesis was conducted using STATISTICA 13.3.721.1 (StatSoft Polska Sp. z.o.o.). Used tests were chi-square, Fisher's exact test (for differences in phenotype), and Mann-Whitney U test (for differences in onset of developmental delay).Results: Browsing returned a total of 973 articles which, after ruling out the repetitions and assessing the inclusion and exclusion criteria, led to final inclusion of 77 articles (337 GPIBD cases) in the analysis. The main outcomes were prevalence of neurological symptoms, onset and semiology of seizures and their response to treatment, and onset of developmental delay. Based on this data a synthesis of phenotypical differences between the groups of GPIBD cases and the general GPIBD cases population was made.Discussion: A synthetical analysis of neurological components in clinical image of GPIBD patients was presented. It highlights the main features of these disorders, which might be useful in clinical practice for consideration in differential diagnosis with children presenting with early-onset seizures and developmental delay. The limitation of this review is the scarcity of the specific data in some reports, concerning the semiology and onset of two main features of GPIBD.

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Prenatal diagnosis of familial recessive PIGN mutation associated with multiple anomalies: A case report

Cited by 7 publications

References 15 publications

PIGNencephalopathy: Characterizing the epileptology

PIGNencephalopathy: Characterizing the epileptology

Damaging novel mutations in PIGN cause developmental epileptic-dyskinetic encephalopathy: a case report

Spectrum of Neurological Symptoms in Glycosylphosphatidylinositol Biosynthesis Defects: Systematic Review

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