Hyperphosphatasia-mental retardation syndrome is a recently delineated disorder associated with a recognizable facial phenotype and brachytelephalangy. This autosomal recessive condition is caused by homozygous and compound heterozygous missense mutations of PIGV, encoding a member of the GPI-anchor biosynthesis pathway. Here, we report on two further, unrelated patients with developmental delay, elevated serum levels of AP, distinctive facial features, hypoplastic terminal phalanges, anal atresia in one and Hirschsprung disease in the other patient. By sequencing PIGV we detected compound heterozygous mutations c.467G>A and c.1022C>A in Patient 1 and a homozygous mutation c.1022C>A in Patient 2. We reviewed the eight reported cases with proven PIGV mutations and re-defined the phenotypic spectrum associated with PIGV mutations: intellectual disability, the distinct facial gestalt, brachytelephalangy, and hyperphosphatasia are constant features but also anorectal malformations and Hirschsprung disease as well as cleft lip/palate and hearing impairment should be considered as part of the clinical spectrum. Moreover, seizures and muscular hypotonia are frequently associated with PIGV mutations.
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http://dx.doi.org/10.1002/ajmg.a.34102 | DOI Listing |
Genes (Basel)
May 2024
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
The case report by Mabry et al. (1970) of a family with four children with elevated tissue non-specific alkaline phosphatase, seizures and profound developmental disability, became the basis for phenotyping children with the features that became known as Mabry syndrome. Aside from improvements in the services available to patients and families, however, the diagnosis and treatment of this, and many other developmental disabilities, did not change significantly until the advent of massively parallel sequencing.
View Article and Find Full Text PDFGenes (Basel)
May 2023
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland.
Congenital disorders of glycosylation (CDGs) are a wide group of genetic diseases characterised by a severe clinical spectrum, consisting of developmental delays, dysmorphisms, and neurological deficits. Mutations in the gene lead to a disorder called hyperphosphatasia with impaired intellectual development syndrome 1 (HPMRS1), distinct from other CDGs in terms of hyperphosphatemia related to abnormal ALP activity and brachytelephalangy. This article discusses the phenotype of six Polish patients with HPMRS1 with a special focus on behavioural and imaging features, which were not addressed in 26 previously reported cases.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2021
Institute for Genomic Statistics and Bioinformatics, University of Bonn, 53127 Bonn, Germany;
Pathogenic germline mutations in lead to glycosylphosphatidylinositol biosynthesis deficiency (GPIBD). Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor pathway exhibit cognitive impairments, motor delay, and often epilepsy. Thus far, the pathophysiology underlying the disease remains unclear, and suitable rodent models that mirror all symptoms observed in human patients have not been available.
View Article and Find Full Text PDFEur J Med Genet
April 2020
Department of Pediatrics, College of Medicine, University of Kentucky, United States.
We report that recessive inheritance of a post-GPI attachment to proteins 2 (PGAP2) gene variant results in the hyperphosphatasia with neurologic deficit (HPMRS) phenotype described by Mabry et al., in 1970. HPMRS, or Mabry syndrome, is now known to be one of 21 inherited glycosylphosphatidylinositol (GPI) deficiencies (IGDs), or GPI biosynthesis defects (GPIBDs).
View Article and Find Full Text PDFBMC Genomics
May 2019
Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, Blichers Allé 20, P. O. Box 50, DK-8830, Tjele, Denmark.
Background: Human milk oligosaccharides (OS) play a key role in brain and gut microbiota development of the neonate, but the underlying biosynthetic steps of OS in the mammary gland are still largely unknown. As bovine milk contains OS with somewhat similar structures and functionalities there is increased interest in further understanding the genetic basis underlying the OS content of milk for eventual extraction and generation of value-added ingredients for infant formulas and nutraceuticals. The present study is the first to report on genetic parameter estimation as well as on a genome wide association study (GWAS) from the largest bovine milk OS dataset analyzed to date.
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