Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders

Fatima Abdelfattah, Ariana Kariminejad, Anne‐Karin Kahlert, Patrick J. Morrison, Evren Gumus, Katherine D. Mathews, Benjamin W. Darbro, David J. Amor, Maie Walsh, Yves Sznajer, Luisa Weiß, Sabine Weidensee, David Chitayat, Patrick Shannon, Eva Bermejo‐Sánchez, Isolina Riaño‐Galán, Ian Hayes, Gemma Poke, Caroline Rooryck, Perrine PennamenSuonavy Khung‐Savatovsky, Annick Toutain, Marie‐Laure Vuillaume, Siavash Ghaderi‐Sohi, Mohamad H. Kariminejad, Sönke Weinert, Heinrich Sticht, Martin Zenker, Denny Schanze

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13 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)1615-1628
Number of pages14
JournalHuman Mutation
Issue number9
Early online date15 Jul 2020
Publication statusPublished - Sept 2020


  • Genetics (clinical)
  • Genetics


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