2026-04-29T15:03:45Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/132962025-03-10T13:26:55Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19616col_20.500.12105_16990
Repisalud author 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 funder German Federal Ministry of Education and Research funder Instituto de Salud Carlos III funder Fundación 1000 sobre Defectos Congénitos 2021-08-17T19:05:09Z 2021-08-17T19:05:09Z 2020 Hum Mutat. 2020 Sep;41(9):1615-1628. 10.1002/humu.24067 1098-1004 Human Mutation 32579715 http://hdl.handle.net/20.500.12105/13296 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. eng Autosomal recessive Genotype–phenotype correlation L-Serine biosynthesis Neu–Laxova syndrome PHGDH PSAT1 Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders research article 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 URL https://repisalud.isciii.es/bitstreams/bb1142fe-1dc3-4fe0-9bfc-7301677b2f07/download File MD5 dd9ea522f11ca7cb2395a699b3f7aab5 1355330 application/pdf ExpandingTheGenotypicAnd_2020.pdf URL https://repisalud.isciii.es/bitstreams/4825e6f3-90c9-4586-8856-2738133bd2de/download File MD5 d3d80e70456ac28e282d038a4bb6316e 3058753 application/pdf ExpandingTheGenotypicAndHumu24067-sup-0001-supp_mat_r1_2020.pdf URL https://repisalud.isciii.es/bitstreams/3ac9d5c4-7287-47ba-9665-93c28121b254/download File MD5 4ba944844e9242d29b9bb82fe05c3c3b 25087 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet ExpandingTheGenotypicAndHumu24067-sup-0002-suppinfo_table_s4_r1-1_2020.xlsx URL https://repisalud.isciii.es/bitstreams/6a14004c-cf14-498f-ad14-a707887d08b9/download File MD5 ab4e0c3a1898d457d830ad845970a0dd 63828 text/plain ExpandingTheGenotypicAnd_2020.pdf.txt URL https://repisalud.isciii.es/bitstreams/2daef61d-ac8b-48dc-bd79-d492e2443585/download File MD5 4bb761f8e9fd13bfc3df629a86760d47 27671 text/plain ExpandingTheGenotypicAndHumu24067-sup-0001-supp_mat_r1_2020.pdf.txt URL https://repisalud.isciii.es/bitstreams/ed80e10a-30f8-4bee-a2ec-2a1da85ed39f/download File MD5 d6a83d55a364aab1204e3d1f21f5bc0c 13722 text/plain ExpandingTheGenotypicAndHumu24067-sup-0002-suppinfo_table_s4_r1-1_2020.xlsx.txt