2024-03-29T13:48:56Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/132962023-10-06T08:59:52Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2102com_20.500.12105_2052col_20.500.12105_16990col_20.500.12105_2103
00925njm 22002777a 4500
dc
Abdelfattah, Fatima
author
Kariminejad, Ariana
author
Kahlert, Anne-Karin
author
Morrison, Patrick J
author
Gumus, Evren
author
Mathews, Katherine D
author
Darbro, Benjamin W
author
Amor, David J
author
Walsh, Maie
author
Sznajer, Yves
author
Weiß, Luisa
author
Weidensee, Sabine
author
Chitayat, David
author
Shannon, Patrick
author
Bermejo-Sanchez, Eva
author
Riaño-Galán, Isolina
author
Hayes, Ian
author
Poke, Gemma
author
Rooryck, Caroline
author
Pennamen, Perrine
author
Khung-Savatovsky, Suonavy
author
Toutain, Annick
author
Vuillaume, Marie-Laure
author
Ghaderi-Sohi, Siavash
author
Kariminejad, Mohamad H
author
Weinert, Sönke
author
Sticht, Heinrich
author
Zenker, Martin
author
Schanze, Denny
author
2020
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.
Hum Mutat. 2020 Sep;41(9):1615-1628.
http://hdl.handle.net/20.500.12105/13296
32579715
10.1002/humu.24067
1098-1004
Human Mutation
Autosomal recessive
Genotype–phenotype correlation
L-Serine biosynthesis
Neu–Laxova syndrome
PHGDH
PSAT1
Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.