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A de novo mutation of SALL4 in a Chinese family with Okihiro syndrome

  • Authors:
    • Xiuli Ma
    • Rui Huang
    • Guo Li
    • Tiesong Zhang
    • Jing Ma
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology, Head and Neck Surgery, Kunming Children's Hospital, Kunming, Yunnan 650228, P.R. China, Department of Otolaryngology, Head and Neck Surgery, Kunming Children's Hospital, Kunming, Yunnan 650228, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 131
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    Published online on: February 17, 2022
       https://doi.org/10.3892/mmr.2022.12647
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Abstract

Okihiro syndrome is an autosomal dominant condition characterized by Duane anomaly and radial ray defects. The present study aimed to analyze the clinical manifestations of a patient with Okihiro syndrome and perform genetic testing on the proband and his family to determine the biological pathogenesis. Clinical data were collected from the proband and his family and genomic DNA was extracted from peripheral blood. Whole exome sequencing was performed by high‑throughput sequencing and mutation sites of the proband and his parents were validated by Sanger sequencing. The proband was diagnosed with Okihiro syndrome, which is characterized by bone abnormality in the arms and hands (radial ray malformation, absence of thumbs) and sensorineural hearing loss. A pathogenic heterozygous c.3060delG variant was identified in exon 4 of spalt‑like transcription factor 4 (SALL4) gene in the proband. This is a frameshift mutation that changes increases the length of SALL4 protein from 1,053 to 1,076 amino acids. The variant was classed as a de novo mutation because the parents of the proband showed no variation at this site. This variant is not included in the ClinVar database and, to the best of our knowledge, has not previously been reported. The de novo heterozygous c.3060delG variant was the molecular pathological cause of Okihiro syndrome in the present study and expanded the database of known SALL4 variants.
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1 

Kohlhase J, Heinrich M, Liebers M, Fröhlich Archangelo L, Reardon W and Kispert A: Cloning and expression analysis of SALL4, the murine homologue of the gene mutated in Okihiro syndrome. Cytogenet Genome Res. 98:274–277. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Kohlhase J, Heinrich M, Schubert L, Liebers M, Kispert A, Laccone F, Turnpenny P, Winter RM and Reardon W: Okihiro syndrome is caused by SALL4 mutations. Hum Mol Genet. 11:2979–2987. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Lim CY, Tam WL, Zhang J, Ang HS, Jia H, Lipovich L, Ng HH, Wei CL, Sung WK, Robson P, et al: Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages. Cell Stem Cell. 3:543–554. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Yang J: SALL4 as a transcriptional and epigenetic regulator in normal and leukemic hematopoiesis. Biomark Res. 6:12018. View Article : Google Scholar : PubMed/NCBI

5 

Miertus J, Borozdin W, Frecer V, Tonini G, Bertok S, Amoroso A, Miertus S and Kohlhase J: A SALL4 zinc finger missense mutation predicted to result in increased DNA binding affinity is associated with cranial midline defects and mild features of Okihiro syndrome. Hum Genet. 119:154–161. 2006. View Article : Google Scholar : PubMed/NCBI

6 

de Celis JF and Barrio R: Regulation and function of Spalt proteins during animal development. Int J Dev Biol. 53:1385–1398. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Hayes A, Costa T and Polomeno RC: The Okihiro syndrome of Duane anomaly, radial ray abnormalities, and deafness. Am J Med Genet. 22:273–280. 1985. View Article : Google Scholar : PubMed/NCBI

8 

Okihiro MM, Tasaki T, Nakano KK and Bennett BK: Duane syndrome and congenital upper-limb anomalies. A familial occurrence. Arch Neurol. 34:174–179. 1977. View Article : Google Scholar : PubMed/NCBI

9 

Alves LU, Perez AB, Alonso LG, Otto PA and Mingroni-Netto RC: Novel frameshift variant in gene SALL4 causing Okihiro syndrome. Eur J Med Genet. 59:80–85. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Kohlhase J, Schubert L, Liebers M, Rauch A, Becker K, Mohammed SN, Newbury-Ecob R and Reardon W: Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy. J Med Genet. 40:473–478. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Terhal P, Rösler B and Kohlhase J: A family with features overlapping Okihiro syndrome, hemifacial microsomia and isolated Duane anomaly caused by a novel SALL4 mutation. Am J Med Genet A. 140:222–226. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Sakaki-Yumoto M, Kobayashi C, Sato A, Fujimura S, Matsumoto Y, Takasato M, Kodama T, Aburatani H, Asashima M, Yoshida N and Nishinakamura R: The murine homolog of SALL4, a causative gene in Okihiro syndrome, is essential for embryonic stem cell proliferation, and cooperates with Sall1 in anorectal, heart, brain and kidney development. Development. 133:3005–3013. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Chen S, Zhou Y, Chen Y and Gu J: Fastp: An ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 34:i884–i890. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Li H and Durbin R: Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 25:1754–1760. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al: 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. Genet Med. 17:405–424. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Swindell SR and Plasterer TN: SEQMAN. Contig assembly. Methods Mol Biol. 70:75–89. 1997.PubMed/NCBI

17 

Jourdain AS, Petit F, Odou MF, Balduyck M, Brunelle P, Dufour W, Boussion S, Brischoux-Boucher E, Colson C, Dieux A, et al: Multiplex targeted high-throughput sequencing in a series of 352 patients with congenital limb malformations. Hum Mutat. 41:222–239. 2020. View Article : Google Scholar : PubMed/NCBI

18 

van de Putte R, Dworschak GC, Brosens E, Reutter HM, Marcelis CLM, Acuna-Hidalgo R, Kurtas NE, Steehouwer M, Dunwoodie SL, Schmiedeke E, et al: A genetics-first approach revealed monogenic disorders in patients with ARM and VACTERL Anomalies. Front Pediatr. 8:3102020. View Article : Google Scholar : PubMed/NCBI

19 

Poznanski AK, Garn SM and Holt JF: The thumb in the congenital malformation syndromes. Radiology. 100:115–129. 1971. View Article : Google Scholar : PubMed/NCBI

20 

Borozdin W, Graham JM Jr, Bohm D, Bamshad MJ, Spranger S, Burke L, Leipoldt M and Kohlhase J: Multigene deletions on chromosome 20q13.13-q13.2 including SALL4 result in an expanded phenotype of Okihiro syndrome plus developmental delay. Hum Mutat. 28:8302007. View Article : Google Scholar : PubMed/NCBI

21 

Borozdin W, Wright MJ, Hennekam RC, Hannibal MC, Crow YJ, Neumann TE and Kohlhase J: Novel mutations in the gene SALL4 provide further evidence for acro-renal-ocular and Okihiro syndromes being allelic entities, and extend the phenotypic spectrum. J Med Genet. 41:e1022004. View Article : Google Scholar : PubMed/NCBI

22 

Parentin F and Perissutti P: Solitary median maxillary central incisor, Duane retraction syndrome, growth hormone deficiency and duplicated thumb phalanx: A case report. Clin Dysmorphol. 12:141–142. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Perez Y, Wormser O, Sadaka Y, Birk R, Narkis G and Birk OS: A Rare Variant in PGAP2 causes autosomal recessive hyperphosphatasia with mental retardation syndrome, with a mild phenotype in heterozygous carriers. Biomed Res Int. 2017:34702342017. View Article : Google Scholar : PubMed/NCBI

24 

Scala M, Mojarrad M, Riazuddin S, Brigatti KW, Ammous Z, Cohen JS, Hosny H, Usmani MA, Shahzad M, Riazuddin S, et al: RSRC1 loss-of-function variants cause mild to moderate autosomal recessive intellectual disability. Brain. 143:e312020. View Article : Google Scholar : PubMed/NCBI

25 

Paradisi I and Arias S: IVIC syndrome is caused by a c.2607delA mutation in the SALL4 locus. Am J Med Genet A. 143:326–332. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Kiefer SM, McDill BW, Yang J and Rauchman M: Murine Sall1 represses transcription by recruiting a histone deacetylase complex. J Biol Chem. 277:14869–14876. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Kiefer SM, Ohlemiller KK, Yang J, McDill BW, Kohlhase J and Rauchman M: Expression of a truncated Sall1 transcriptional repressor is responsible for Townes-Brocks syndrome birth defects. Hum Mol Genet. 12:2221–2227. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Al-Baradie R, Yamada K, St Hilaire C, Chan WM, Andrews C, McIntosh N, Nakano M, Martonyi EJ, Raymond WR, Okumura S, et al: Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet. 71:1195–1199. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Kiefer SM, Robbins L, Barina A, Zhang Z and Rauchman M: SALL1 truncated protein expression in Townes-brocks syndrome leads to ectopic expression of downstream genes. Hum Mutat. 29:1133–1140. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Liberalesso PBN, Cordeiro ML, Karuta SCV, Koladicz KRJ, Nitsche A, Zeigelboim BS, Raskin S and Rauchman M: Phenotypic and genotypic aspects of Townes-Brock syndrome: Case report of patient in southern Brazil with a new SALL1 hotspot region nonsense mutation. BMC Med Genet. 18:1252017. View Article : Google Scholar : PubMed/NCBI

31 

Miettinen M, Wang Z, McCue PA, Sarlomo-Rikala M, Rys J, Biernat W, Lasota J and Lee YS: SALL4 expression in germ cell and non-germ cell tumors: A systematic immunohistochemical study of 3215 cases. Am J Surg Pathol. 38:410–420. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Becker R, Horn D, Knoll U, Stumm M, Wegner RD, Peters H and Sarioglu N: First-trimester prenatal diagnosis of Okihiro syndrome. Fetal Diagn Ther. 27:222–226. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Li B, Chen S, Sun K, Xu R and Wu Y: Genetic analyses identified a SALL4 gene mutation associated with holt-oram syndrome. DNA Cell Biol. 37:398–404. 2018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ma X, Huang R, Li G, Zhang T and Ma J: A <em>de novo</em> mutation of <em>SALL4</em> in a Chinese family with Okihiro syndrome. Mol Med Rep 25: 131, 2022.
APA
Ma, X., Huang, R., Li, G., Zhang, T., & Ma, J. (2022). A <em>de novo</em> mutation of <em>SALL4</em> in a Chinese family with Okihiro syndrome. Molecular Medicine Reports, 25, 131. https://doi.org/10.3892/mmr.2022.12647
MLA
Ma, X., Huang, R., Li, G., Zhang, T., Ma, J."A <em>de novo</em> mutation of <em>SALL4</em> in a Chinese family with Okihiro syndrome". Molecular Medicine Reports 25.4 (2022): 131.
Chicago
Ma, X., Huang, R., Li, G., Zhang, T., Ma, J."A <em>de novo</em> mutation of <em>SALL4</em> in a Chinese family with Okihiro syndrome". Molecular Medicine Reports 25, no. 4 (2022): 131. https://doi.org/10.3892/mmr.2022.12647
Copy and paste a formatted citation
x
Spandidos Publications style
Ma X, Huang R, Li G, Zhang T and Ma J: A <em>de novo</em> mutation of <em>SALL4</em> in a Chinese family with Okihiro syndrome. Mol Med Rep 25: 131, 2022.
APA
Ma, X., Huang, R., Li, G., Zhang, T., & Ma, J. (2022). A <em>de novo</em> mutation of <em>SALL4</em> in a Chinese family with Okihiro syndrome. Molecular Medicine Reports, 25, 131. https://doi.org/10.3892/mmr.2022.12647
MLA
Ma, X., Huang, R., Li, G., Zhang, T., Ma, J."A <em>de novo</em> mutation of <em>SALL4</em> in a Chinese family with Okihiro syndrome". Molecular Medicine Reports 25.4 (2022): 131.
Chicago
Ma, X., Huang, R., Li, G., Zhang, T., Ma, J."A <em>de novo</em> mutation of <em>SALL4</em> in a Chinese family with Okihiro syndrome". Molecular Medicine Reports 25, no. 4 (2022): 131. https://doi.org/10.3892/mmr.2022.12647
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