PIGO deficiency: palmoplantar keratoderma and novel mutations

Morren, Marie; Jaeken, Jaak; Visser, Gepke; Salles, Isabelle I.; Geet, Chris Van; Simeoni, Ilenia; Turro, Ernest; Freson, Kathleen

doi:10.1186/s13023-017-0654-9

Cited by 13 publications

(11 citation statements)

References 27 publications

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“…Psychomotor delay, ID, and variable AP elevation are the only consistent features of all individuals with pathogenic mutations in PIGV [ 9 , 28 – 34 ], PIGO [ 7 , 16 , 17 , 31 , 35 – 37 ], PGAP2 [ 4 , 8 , 18 , 38 ], PGAP3 [ 5 , 19 , 39 – 41 ], and PIGY [ 6 ]. Speech development, especially expressive language, is more severely affected than motor skills in the majority of the affected individuals (Table 1 ).…”

Section: Methodsmentioning

confidence: 99%

Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis

Knaus

Pantel

Pendziwiat³

et al. 2018

Genome Med

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BackgroundGlycosylphosphatidylinositol biosynthesis defects (GPIBDs) cause a group of phenotypically overlapping recessive syndromes with intellectual disability, for which pathogenic mutations have been described in 16 genes of the corresponding molecular pathway. An elevated serum activity of alkaline phosphatase (AP), a GPI-linked enzyme, has been used to assign GPIBDs to the phenotypic series of hyperphosphatasia with mental retardation syndrome (HPMRS) and to distinguish them from another subset of GPIBDs, termed multiple congenital anomalies hypotonia seizures syndrome (MCAHS). However, the increasing number of individuals with a GPIBD shows that hyperphosphatasia is a variable feature that is not ideal for a clinical classification.MethodsWe studied the discriminatory power of multiple GPI-linked substrates that were assessed by flow cytometry in blood cells and fibroblasts of 39 and 14 individuals with a GPIBD, respectively. On the phenotypic level, we evaluated the frequency of occurrence of clinical symptoms and analyzed the performance of computer-assisted image analysis of the facial gestalt in 91 individuals.ResultsWe found that certain malformations such as Morbus Hirschsprung and diaphragmatic defects are more likely to be associated with particular gene defects (PIGV, PGAP3, PIGN). However, especially at the severe end of the clinical spectrum of HPMRS, there is a high phenotypic overlap with MCAHS. Elevation of AP has also been documented in some of the individuals with MCAHS, namely those with PIGA mutations. Although the impairment of GPI-linked substrates is supposed to play the key role in the pathophysiology of GPIBDs, we could not observe gene-specific profiles for flow cytometric markers or a correlation between their cell surface levels and the severity of the phenotype. In contrast, it was facial recognition software that achieved the highest accuracy in predicting the disease-causing gene in a GPIBD.ConclusionsDue to the overlapping clinical spectrum of both HPMRS and MCAHS in the majority of affected individuals, the elevation of AP and the reduced surface levels of GPI-linked markers in both groups, a common classification as GPIBDs is recommended. The effectiveness of computer-assisted gestalt analysis for the correct gene inference in a GPIBD and probably beyond is remarkable and illustrates how the information contained in human faces is pivotal in the delineation of genetic entities.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0510-5) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis

Knaus

Pantel

Pendziwiat³

et al. 2018

Genome Med

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show abstract

“…Psychomotor delay, ID and variable AP elevation are the only consistent features of all individuals with pathogenic mutations in PIGV [9, 27-33], PIGO [7, 16, 17, 30, 34-36], PGAP2 [4, 8, 18, 37], PGAP3 [5, 19, 38-40], PIGW [3, 41], and PIGY [6]. Speech development, especially expressive language, is more severely affected than motor skills in the majority of the affected individuals (Table S1).…”

Section: Methods and Study Designmentioning

confidence: 99%

Characterization of Glycosylphosphatidylinositol Biosynthesis Defects by Clinical Features, Flow Cytometry, and Automated Image Analysis

Knaus

Pantel

Pendziwiat³

et al. 2017

Preprint

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“…Moreover, Morren and al. also described a patient with PIGO mutations and psychomotor disability, epilepsy, palmoplantar keratoderma, hyperphosphatasia and platelet dysfunction [ 82 ]. The biochemical basis explaining this dermatologic phenotype in patients with GPI-AP defects remains to be established.…”

Section: Resultsmentioning

confidence: 99%

A step closer in defining glycosylphosphatidylinositol anchored proteins role in health and glycosylation disorders

Manea

2018

Molecular Genetics and Metabolism Reports

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Glycosylphosphatidylinositol anchored proteins (GPI-APs) represent a class of soluble proteins attached to the external leaflet of the plasma membrane by a post-translation modification, the GPI anchor. The 28 genes currently involved in the synthesis and remodelling of the GPI anchor add to the ever-growing class of congenital glycosylation disorders. Recent advances in next generation sequencing technology have led to the discovery of Mabry disease and CHIME syndrome genetic aetiology. Moreover, with each described mutation known phenotypes expand and new ones emerge without clear genotype-phenotype correlation. A protein database search was made for human GPI-APs with defined pathology to help building-up a physio-pathological mechanism from a clinical perspective. GPI-APs function in vitamin-B6 and folate transport, nucleotide metabolism and lipid homeostasis. Defining GPI-APs role in disease bears significant clinical implications.

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PIGO deficiency: palmoplantar keratoderma and novel mutations

Cited by 13 publications

References 27 publications

Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis

Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis

Characterization of Glycosylphosphatidylinositol Biosynthesis Defects by Clinical Features, Flow Cytometry, and Automated Image Analysis

A step closer in defining glycosylphosphatidylinositol anchored proteins role in health and glycosylation disorders

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