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.

Background: There is a strong evidence for genetic factors as the main causes of Autism Spectrum Disorders (ASD). To date, hundreds of genes have been identified either by copy number variations (CNVs) and/or single nucleotide variations. However, despite all the findings, the genetics of these disorders have not been totally explored.Methods: Thus, the aim of our work was to identify rare CNVs and genes present in these regions in ASD children, using a high‐resolution comparative genomic hybridization technique and quantitative PCR (qPCR) approach.Results: Our results have shown 60–70 chromosomal aberrations per patient. We have initially selected 66 CNVs that have been further assessed using qPCR. Finally, we have validated 22 CNVs including 11 deletions and 11 duplications. Ten CNVs are de novo, 11 are inherited and one of unknown origin of transmission. Among the CNVs detected, novel ASD candidate genes PJA2, SYNPO, APCS, and TAC1 have been identified in our group of Lebanese patients. In addition, previously described CNVs have been identified containing genes such as SHANK3, MBP, CHL1, and others.Conclusion: Our study broadens the population spectrum of studied ASD patients and adds new candidates at the list of genes contributing to these disorders.

Simpson-Golabi-Behmel syndrome (SGBS). 312870. GPC3. 300037. Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in the GPC3 gene(s) in