SHORT syndrome with microcephaly and developmental delay.

Autor: Patel V; North West Thames Regional Genetics Service, NHS, Northwick Park & St Mark's Hospitals, London, Harrow, UK., Cui W; Faculty of Medicine, Department of Metabolism, Digestions and Reproduction, Imperial College London, London, UK., Cobben JM; North West Thames Regional Genetics Service, NHS, Northwick Park & St Mark's Hospitals, London, Harrow, UK.; Faculty of Medicine, Department of Metabolism, Digestions and Reproduction, Imperial College London, London, UK.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2023 Mar; Vol. 191 (3), pp. 850-854. Date of Electronic Publication: 2022 Dec 14.
DOI: 10.1002/ajmg.a.63078
Abstrakt: We report a boy with typical clinical features of SHORT syndrome alongside a significant microcephaly and severe developmental delay associated with a de novo single nucleotide missense DNA variant resulting in a single amino acid change in codon 486 of the PIK3R1 gene (PIK3R1 c.1456G>A (p.Ala486Thr)). Our report strikingly coincides with another recently published case from Brazil, describing a 23-year-old woman with the same de novo PIK3R1 DNA variant, who also exhibits SHORT syndrome with severe secondary microcephaly and intellectual disability. On review of the literature, we have identified further cases of PIK3R1-related SHORT Syndrome with a similar phenotype. We note all these cases (including ours) have variants located in the -inter SH2 domain (iSH2); we speculate that pathogenic iSH2 located PIK3R1 variants are associated with a different and otherwise unreported clinical picture of SHORT syndrome that presents with microcephaly and/or significant developmental delay/intellectual disability. The pathogenic mechanism of why these variants apparently lead to a different clinical picture of SHORT syndrome remains unknown.
(© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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