SOX5: Lamb-Shaffer syndrome-A case series further expanding the phenotypic spectrum.
Lamb-Shaffer
SOX5
global delay
neurodevelopment
speech delay
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
13
12
2022
received:
19
08
2022
accepted:
28
12
2022
medline:
10
4
2023
pubmed:
3
3
2023
entrez:
2
3
2023
Statut:
ppublish
Résumé
To delineate further the clinical phenotype of Lamb-Shaffer Syndrome (LSS) 16 unpublished patients with heterozygous variation in SOX5 were identified either through the UK Decipher database or the study team was contacted by clinicians directly.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.
Identifiants
pubmed: 36861937
doi: 10.1002/ajmg.a.63124
doi:
Substances chimiques
Nucleotides
0
SOX5 protein, human
0
SOXD Transcription Factors
0
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1447-1458Subventions
Organisme : Wellcome Trust
ID : WT223718/Z/21/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT098051
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
Apple app store. (Accessed Nov 11, 2020). https://apps.apple.com/gb/app/growth-charts-uk-who/id916579608
Decipher. (Accessed November 14, 2022). https://www.deciphergenomics.org/patient/264625/genotype/193098/protein
Ellard, S., Baple, E. L., Callaway, A., Berry, I., Forrester, N., Turnbull, C., Owens, M., Eccles, D. M., Abbs, S., Scott, R., Deans, Z. C., Lester, T., Campbell, J., Newman, W. G., Ramsden, S., & McMullan, D. J. (2020). ACGS best practice guidelines for variant classification in rare disease 2020. Association for Clinical Genomic Science (ACGS).
Firth, H. V., Richards, S. M., Bevan, A. P., Clayton, S., Corpas, M., Rajan, D., Vooren, S. V., Moreau, Y., Pettett, R. M., & Carter, N. P. (2009). DECIPHER: Database of chromosomal imbalance and phenotype in humans using Ensembl resources. American Journal of Human Genetics, 84, 524-533. https://doi.org/10/1016/j.ajhg.2009.03.010
Fukushi, D., Kenichiro, Y., Suzuki, K., Inaba, M., Nomura, N., Suzuki, Y., Katoh, K., Mizuno, S., & Wakamatsu, N. (2018). Clinical and genetic characterization of a patient with SOX5 haploinsufficiency caused by a de novo balanced reciprocal translocation. Gene, 655, 65-70.
Huang, N., Lee, I., Marcotte, E. M., & Hurles, M. E. (2010). Characterising and predicting haploinsufficiency in the human genome. PLoS Genetics, 6, e1001154.
Ikeda, T., Zhang, J., Chano, T., Mabuchi, A., Fukuda, A., Kawaguchi, H., Nakamura, K., & Ikegawa, S. (2002). Identification and characterization of the human long form of Sox5 (L-SOX5) gene. Gene, 298, 59-68.
KondohH, K. Y. (2013). Sox proteins: Regulators of cell fate specification and differentiation. Development, 140, 4129-4144.
Lamb, A. N., Rosenfeld, J. A., Neill, N. J., Talkowski, M. E., Blumenthal, I., Girirajan, S., Keelean-Fuller, D., Fan, Z., Pouncey, J., Stevens, C., Mackay-Loder, L., Terespolsky, D., Bader, P. I., Rosenbaum, K., Vallee, S. E., Moeschler, J. B., Ladda, R., Sell, S., Martin, J., … Shaffer, L. G. (2012). Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behaviour problems, and mild dysmorphic features. Human Mutation, 33, 728-740.
Lee, R. W., Bodurtha, J., Cohen, J., Fatemi, A., & Batista, D. (2013). Deletion 12q12 involving SOX5 in two children with developmental delay and dysmorphic features. Pediatric Neurology, 48(4), 317-320.
Lefebvre, V. (2010). The SOxD transcription factors-Sox5, Sox6, and Sox13-Are key cell fate modulators. The International Journal of Biochemistry and Cell Biology., 42, 429-432.
Nesbitt, A., Bhoj, E. J., Gibson, K. M., Yu, Z., Denenberg, E., Sarmady, M., Tischler, T., Cao, K., Dubbs, H., Zackai, E. H., & Santani, A. (2015). Exome sequencing expands the mechanism of SOX5-associated intellectual disability: A case presentation with review of SOX-related disorders. American Journal of Medical Genetics AJMG, 167A(11), 2548-2554.
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., Rehm, H. L., & ACMG Laboratory Quality Assurance Committee. (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405-424.
Riggs, E. R., Andersen, E. F., Cherry, A. M., Kantarci, S., Kearney, H., Patel, A., Raca, G., Ritter, D. I., South, S. T., Thorland, E. C., Pineda-Alvarez, D., Aradhya, S., & Martin, C. L. (2020). Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genetics in Medicine, 22(2), 245-257.
Schanze, I., Schanze, D., Bacino, C. A., Douzgou, S., Kerr, B., & Zenker, M. (2013). Haploinsufficiency of SOX5, a member of the SOX (SRY-related HMG-box) family of transcription factors is a cause of intellectual disability. European Journal of Medical Genetics., 56(2), 108-113.
Walker, M., & Armfield, A. (1981). What is the Makaton vocabulary? Special Education: Forward Trends, 8(3), 19-20 PMID: 6458105.
Zawerton, A., Mignot, C., Sigafoos, A., Blackburn, P. R., Haseeb, A., McWalter, K., Ichikawa, S., Nava, C., Keren, B., Charles, P., Marey, I., Tabet, A.-C., Levy, J., Perrin, J., Hartmann, A., Lesca, J., Schluth-Bolard, C., Monin, P., Dupuis-Girod, S., … Depienne, C. (2019). Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency. Genetics in Medicine, 22, 524-537.