SOX5: Lamb–Shaffer syndrome—A case series further expanding the phenotypic spectrum

Katharine Edgerley, Lisa Bryson, Lucy Hanington, Rachel Irving, Shelagh Joss, Anne Lampe, Isabelle Maystadt, Deborah Osio, Ruth Richardson, Miranda Splitt, Francis H Sansbury, Ingrid Scurr, Helen Stewart, Alisdair McNeil, Karen J Low*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)
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Abstract

To delineate further the clinical phenotype of Lamb–Shaffer Syndrome (LSS) 16 unpublished patients with heterozygous variation in SOX5 were identified either through the UK Decipher database or the study team was contacted by clinicians directly. Clinical phenotyping tables were completed for each patient by their responsible clinical geneticist. Photos and clinical features were compared to assess key phenotypes and genotype–phenotype correlation. We report 16 SOX5 variants all of which meet American College of Medical Genetics/Association for Clinical Genomic Science ACMG/ACGS criteria class IV or V. 7/16 have intragenic deletions of SOX5 and 9/16 have single nucleotide variants (including both truncating and missense variants). The cohort includes two sets of monozygotic twins and parental gonadal mosaicism is noted in one family. This cohort of 16 patients is compared with the 71 previously reported cases and corroborates previous phenotypic findings. As expected, the most common findings include global developmental delay with prominent speech delay, mild to moderate intellectual disability, behavioral abnormalities and sometimes subtle characteristic facial features. We expand in more detail on the behavioral phenotype and observe that there is a greater tendency toward lower growth parameters and microcephaly in patients with single nucleotide variants. This cohort provides further evidence of gonadal mosaicism in SOX5 variants; this should be considered when providing genetic counseling for couples with one affected child and an apparently de novo variant.
Original languageEnglish
Pages (from-to)1447-1458
Number of pages12
JournalAmerican Journal of Medical Genetics, Part A
Volume191
Issue number5
Early online date2 Mar 2023
DOIs
Publication statusPublished - 7 Apr 2023

Bibliographical note

Funding Information:
This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data are available from https://deciphergenomics.org/about/stats and via email from contact@deciphergenomics.org . Funding for the DECIPHER project was provided by Wellcome (grant number WT223718/Z/21/Z). The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF‐1009‐003], a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute [grant number WT098051]. The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.

Funding Information:
This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data are available from https://deciphergenomics.org/about/stats and via email from contact@deciphergenomics.org. Funding for the DECIPHER project was provided by Wellcome (grant number WT223718/Z/21/Z). The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF-1009-003], a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute [grant number WT098051]. The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.

Publisher Copyright:
© 2023 Wiley Periodicals LLC.

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