Identification of Oliver-McFarlane syndrome caused by novel compound heterozygous variants of PNPLA6

Liu, Fan; Ji, Yiming; Li, Guimei; Xu, Chao; Sun, Yan

doi:10.1016/j.gene.2020.145027

Cited by 12 publications

(8 citation statements)

References 30 publications

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“…Analysis including the conservation of nucleotide bases and amino acids, the frequency of the normal population (1000 Genomes Project, ExAC, dbSNP database and locus specific databases), as well as the use of data from Human Gene Mutation Database (HGMD), ClinVar database, and Online Mendelian Inheritance in Man (OMIM), were performed by NextGene V2.3.4 software and lab’s own scripts [ 13 ]. The potential deleterious effects and biological function of the mutation were predicted using SIFT ( http://sift.jcvi.org ), PolyPhen-2 ( http://genetics.bwh.harvard.edu/pph2/ ), and Mutation Taster ( http://www.mutationtaster.org/ ).…”

Section: Methodsmentioning

confidence: 99%

A novel mutation in the PRPH2 gene in a Chinese pedigree with retinitis pigmentosa and angle-closure glaucoma

Zhang

et al. 2021

BMC Ophthalmol

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Background Retinitis pigmentosa (RP) is a rare, progressive, and hereditary disorder that leads to the progressive loss of vision and visual field, and in some cases blindness. The specific relationship between RP and glaucoma has been debated for decades. Methods In this study, we examined a Han RP family with concomitant angle-closure glaucoma (ACG), performed an inductive analysis of their clinical features and assistant results, and applied whole-exome sequencing (WES) technology for a molecular diagnosis. Results A novel transversion mutation (c.626 T > A) was identified in the peripherin-2 (PRPH2) gene in the proband, resulting in the substitution of Valine to aspartic acid in codon 209. A full ophthalmic examination showed that the proband with the c.626 T > A mutation had a typical RP manifestation, with close angles; however, the proband’s elder brother, who lacked the novel mutation, had a normal fundus and open angles. Conclusion Our results extend the genetic mutation spectrum of PRPH2 in RP, and provide evidence to support a genetic correlation between RP and ACG.

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Section: Methodsmentioning

confidence: 99%

A novel mutation in the PRPH2 gene in a Chinese pedigree with retinitis pigmentosa and angle-closure glaucoma

Zhang

et al. 2021

BMC Ophthalmol

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“…In contrast, the effector domains of CAP family transcription factors include CAP (cAMP receptor protein (CRP), CooA (heme-containing CO sensor), and FNR (fumarate and nitrate reduction). This will lead to conformational changes and activate transcription (Chan, 2000;Liu et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome

Liu²,

Liu

et al. 2022

Front. Genet.

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Background: Boucher–Neuhäuser syndrome (BNS, MIM 215470) is a rare autosomal recessive syndrome caused by mutations in the PNPLA6 gene. Few BNS cases have been reported for functional validation at the RNA level. Herein, we report on the family of a 17-year-old girl with clinical characteristics of BNS, genetic validation, and a systematic review of PNPLA6 variants related to BNS.Methods: Clinical data and blood samples were collected from the patient and their parents, and whole-exome sequencing was performed and confirmed by Sanger sequencing. RNA-sequencing (RNA-Seq) and quantitative RT-PCR (qRT-PCR) were performed, and the three-dimensional protein structures of the variants were predicted.Results: We report a 17-year-old female with progressive night blindness since the age of four, primary amenorrhea, and non-development of secondary sexual characteristics. Her impaired vision was diagnosed as retinal pigmentary degeneration of the retina. She had congenital hypogonadotropic hypogonadism (CHH) but no cerebellar ataxia at present. Two novel compound heterozygous variants (c.2241del/p.Met748TrpfsTer65 and c.2986A>G/p.Thr996Ala) of the PNPLA6 gene (NM_006702.4) were identified by whole-exome sequencing. The former variant was carried from her healthy father and has not been reported previously. The latter was inherited from her healthy mother and was noted in a report without functional studies. The RT-PCR results showed that the mRNA expression of PNPLA6 was lower in this patient and her father than in the control group. She was diagnosed with BNS. Both variants (c.2241del and c.2986A>G) were likely pathogenic according to the ACMG criteria. The novel variants in the PNPLA6 gene related to Boucher–Neuhäuser syndrome were summarized in this article.Conclusion: The possibility of Boucher–Neuhäuser syndrome should be considered when patients present with night blindness, impaired vision, and hypogonadotropic hypogonadism. Gene sequencing is currently the primary diagnostic method. Herein, novel compound heterozygous variants of PNPLA6 were identified in a BNS patient, and its function was verified at the RNA level. The PNPLA6 c.2241del variant is novel and potentially pathogenic, expanding the mutation spectrum in PNPLA6.

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“…Analysis including the conservation of nucleotide bases and amino acids, the frequency of the normal population (1000 Genomes Project, ExAC, dbSNP database and locus speci c databases), as well as the use of data from Human Gene Mutation Database (HGMD), ClinVar database, and Online Mendelian Inheritance in Man (OMIM), were performed by NextGene V2.3.4 software [13]. The potential deleterious effects and biological function of the mutation were predicted using SIFT (http://sift.jcvi.org), PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org/).…”

Section: Bioinformatics Analysismentioning

confidence: 99%

A Novel Mutation in the PRPH2 Gene in a Chinese Pedigree with Retinitis Pigmentosa and Angle-closure Glaucoma

Zhang

et al. 2021

Preprint

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Background: Retinitis pigmentosa (RP) is a rare, progressive, and hereditary disorder that leads to the progressive loss of vision and visual field, and in some cases blindness. The specific relationship between RP and glaucoma has been debated for decades.Methods: In this study, we examined a Han RP family with concomitant angle-closure glaucoma (ACG), performed an inductive analysis of their clinical features and assistant results, and applied whole-exome sequencing (WES) technology for a molecular diagnosis. Results: A novel transversion mutation (c.626T>A) was identified in the peripherin-2 (PRPH2) gene in the proband, resulting in the substitution of tyrosine to aspartic acid in codon 209. A full ophthalmic examination showed that the proband with the c.626T>A mutation had a typical RP manifestation, with close angles; however, the proband’s elder brother, who lacked the novel mutation, had a normal fundus and open angles. Conclusion: Our results extend the genetic mutation spectrum of PRPH2 in RP, and provide evidence to support a genetic correlation between RP and ACG.

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Identification of Oliver-McFarlane syndrome caused by novel compound heterozygous variants of PNPLA6

Cited by 12 publications

References 30 publications

A novel mutation in the PRPH2 gene in a Chinese pedigree with retinitis pigmentosa and angle-closure glaucoma

A novel mutation in the PRPH2 gene in a Chinese pedigree with retinitis pigmentosa and angle-closure glaucoma

Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome

A Novel Mutation in the PRPH2 Gene in a Chinese Pedigree with Retinitis Pigmentosa and Angle-closure Glaucoma

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