Journal article
Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders
Human mutation, Vol.41(9), pp.1615-1628
09/2020
DOI: 10.1002/humu.24067
PMID: 32579715
Abstract
Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu–Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre‐ or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease‐causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.
Dimeric PSAT1 structure with the bound pyridoxal 5′‐phosphate shown in stick presentation. In one subunit, variants associated with lethal and nonlethal phenotypes are highlighted by red and orange balls, respectively
Details
- Title: Subtitle
- Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders
- Creators
- Fatima Abdelfattah - University Hospital MagdeburgAriana Kariminejad - Kariminejad‐Najmabadi Pathology and Genetics CenterAnne‐Karin Kahlert - University Hospital Schleswig‐HolsteinPatrick J Morrison - Queen's University BelfastEvren Gumus - School of Medicine, Harran UniversityKatherine D Mathews - University of IowaBenjamin W Darbro - University of IowaDavid J Amor - Royal Children's HospitalMaie Walsh - Royal Children's HospitalYves Sznajer - Université Catholique de LouvainLuisa Weiß - Technische Universität DresdenSabine Weidensee - Human Medical GeneticsDavid Chitayat - University of TorontoPatrick Shannon - University of TorontoEva Bermejo‐Sánchez - ECEMC (Spanish Collaborative Study of Congenital Malformations), Research Unit on Congenital Anomalies (UIAC), Institute of Rare Diseases Research (IIER), Institute of Health Carlos III, Ministry of Science and InnovationIsolina Riaño‐Galán - CIBER de Epidemiologia y Salud PúblicaIan Hayes - Auckland HospitalGemma Poke - Genetic Health Service New Zealand, Wellington Regional HospitalCaroline Rooryck - University of BordeauxPerrine Pennamen - University of BordeauxSuonavy Khung‐Savatovsky - Hôpital Universitaire Robert‐DebréAnnick Toutain - Université de Tours, INSERMMarie‐Laure Vuillaume - Université de Tours, INSERMSiavash Ghaderi‐Sohi - Kariminejad‐Najmabadi Pathology and Genetics CenterMohamad H Kariminejad - Kariminejad‐Najmabadi Pathology and Genetics CenterSönke Weinert - University Hospital MagdeburgHeinrich Sticht - Friedrich‐Alexander‐Universität Erlangen‐NürnbergMartin Zenker - University Hospital MagdeburgDenny Schanze - University Hospital Magdeburg
- Resource Type
- Journal article
- Publication Details
- Human mutation, Vol.41(9), pp.1615-1628
- DOI
- 10.1002/humu.24067
- PMID
- 32579715
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Number of pages
- 14
- Grant note
- Fundación 1000 sobre Defectos Congénitos, Spain Institute of Health Carlos III: Convenio ISCIII‐ASEREMAC Bundesministerium für Bildung und Forschung (GeNeRARe; FKZ: 01GM1902A)
- Language
- English
- Date published
- 09/2020
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Neurology (Pediatrics)
- Record Identifier
- 9984070484102771
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