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| Intellectual disability - microarray and sequencing v2.978 | PIGG |
Catherine Snow Source Expert Review Green was added to PIGG. Added phenotypes Mental retardation, autosomal recessive 53, 616917 for gene: PIGG Publications for gene PIGG were changed from 26996948; 28581210 to 28581210; 26996948; 30914295 Rating Changed from No List (delete) to Green List (high evidence) |
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| Intellectual disability - microarray and sequencing v2.510 | PIGG |
Konstantinos Varvagiannis gene: PIGG was added gene: PIGG was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: PIGG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGG were set to 26996948; 28581210 Phenotypes for gene: PIGG were set to # 616917 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 53; MRT53 Penetrance for gene: PIGG were set to Complete Review for gene: PIGG was set to GREEN gene: PIGG was marked as current diagnostic Added comment: PMID: 26996948 reports on 5 individuals from 3 families, with biallelic pathogenic variants in PIGG. Individuals from first family, were born to consanguineous parents from Egypt and were homozygous for a stopgain variant [p.(Gln310*)]. The patient from the second family had a rare missense SNV [p.(Arg669Cys)] and a de novo microdeletion affecting PIGG on her other allele. In the third family (consanguineous parents from Pakistan), two affected sibs were found to be homozygous for a splice variant. The phenotype consisted of hypotonia, early-onset seizures and intellectual disability. Ataxia was an additional feature in one of the families. Seizures, were observed in most of patients but do not appear to be a universal feature as they were absent in one of the sibs from the third family (10 years of age), while the other had a single episode by the age of 12 years. In vitro testing of lymphoblastoid cell lines (generated from individuals from the 1st and 3rd family) indicated that the variants abolished completely the function of PIGG, whereas the surface level of GPI anchored proteins was normal. // PMID: 28581210 describes the phenotype of 2 sibs from Palestine, homozygous for a stopgain variant [p.(Trp547*)]. Hypotonia, feeding difficulties, severe non-progressive ataxia (with cerebellar hypoplasia), intellectual disability and seizures were common features. Differences in severity and/or additional features might be explained by other homozygous variants (the girl had a concurrent diagnosis of MCAD deficiency). The authors demonstrated that the PIGG transcript levels were significantly lower (approximately half) in the two siblings compared to their parents, while the transcripts with the mutation in the heterozygous parents were very low due to nonsense-mediated decay. Patient fibroblasts showed decreased surface level of GPI-anchored proteins, in contrast with what was noted in lymphoblastoid cells in the previous study. // PIGG has been included in gene panels for intellectual disability offered by different diagnostic labs. // As a result this gene can be considered for inclusion in this panel as green (or amber). Sources: Literature, Expert Review |
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