Related Experiment Video

Updated: Jan 26, 2026

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells

Published on: March 10, 2023

Lethal perinatal hypophosphatasia caused by a novel compound heterozygous mutation: a case report

Fengdan Yu¹, Junyi Wang², Xiaojing Xu¹

¹Department of Neonatal Intensive Care Unit, The First Hospital of Tsinghua University, No. 6, Jiuxianqiao, Chaoyang District, Beijing, 100016, China.

|April 14, 2019

Abstract

Background:

Hypophosphatasia (HPP) is a rare hereditary disorder characterized by defective bone and tooth mineralization and deficiency of tissue non-specific alkaline phosphatase (TNAP) activity. The clinical presentation of HPP is highly variable, and the prognosis for the infantile form is poor.

Case Presentation:

This study reports a male infant diagnosed with lethal perinatal HPP. His gene analysis showed two heterozygous missense variants c.406C > T (p.R136C) and c.461C > T (p.A154V). The two mutations originated separately from his parents, consistent with autosomal recessive perinatal HPP, and the c.461C > T (p.A154V) was the novel mutation. Three-level structure model provide an explanation of the two mutated alleles correlating with the lethal phenotype of our patient. Results of SIFT, PolyPhen_2, and REVEL showed two mutations were pathogenic.

Conclusions:

We demonstrated a case of perinatal lethal HPP caused by two heterozygous mutations, and one of which was novel. This finding will prove relevant for genetic counseling and perinatal gene testing for affected families.

Keywords:

Gene mutation Hypophosphatasia Tissue non-specific alkaline phosphatase

More Related Videos

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

Lethality Bioassay Using Artemia salina L.

Lethality Bioassay Using Artemia salina L.

Published on: October 11, 2022

Related Concept Videos

Mutations

Mutations

Mutations

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...

Lethal Alleles

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...

Viral Mutations

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...

Mutation, Gene Flow, and Genetic Drift

Mutation, Gene Flow, and Genetic Drift

In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).

Molecules and Compounds

Molecules and Compounds

Atoms and Molecules

Articles linked to this work by shared authors, journal, and citation graph.

One-pot synthesized inverse-structured CeO2/Ni catalysts for enhanced low-temperature CO2 methanation via metal-support interactions.

Journal of colloid and interface science·2026

Pramocaine hydrochloride potentiates fluconazole against Candida albicans biofilms by targeting Erg12 and inhibiting ubiquinone biosynthesis.

Biochemical pharmacology·2026

Disruption of the UPC2 Gene Enhances Fluconazole Antifungal Activity by Inhibiting HAC1 mRNA Splicing in Candida albicans.

Pathogens (Basel, Switzerland)·2026

A multilevel probabilistic dose response model for radiation-induced Harderian gland tumor prevalence-single beam and mixed field effects.

Life sciences in space research·2026

Recombinant subunit vaccines against invasive fungal infections: mechanisms, development progress, and therapeutic potential.

Vaccine·2026

A clinico-radiological model integrating baseline CT-derived body composition to predict prognosis in immunotherapy-treated metastatic colorectal cancer.

European journal of radiology·2026

See all related articles