Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome.

Vodopiutz, J; Zoller, H; Fenwick, A; Arnhold, R; Schmid, M; Prayer, D; Müller, T; Repa, A; Pollak, A; Aufricht, C; Wilkie, A; Janecke, A

Journal article

Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome.

Abstract:: OBJECTIVE: To delineate a novel autosomal recessive multiple congenital anomaly-mental retardation (MCA-MR) syndrome in 2 female siblings of a consanguineous pedigree and to identify the disease-causing mutation. STUDY DESIGN: Both siblings were clinically characterized and homozygosity mapping and sequencing of candidate genes were applied. The contribution of nonsense-mediated messenger RNA (mRNA) decay to the expression of mutant mRNA in fibroblasts of a healthy carrier and a control was studied by pyrosequencing. RESULTS: We identified the first homozygous SALL1 mutation, c.3160C > T (p.R1054*), in 2 female siblings presenting with multiple congenital anomalies, central nervous system defects, cortical blindness, and absence of psychomotor development (ie, a novel recognizable, autosomal recessive MCA-MR). The mutant SALL1 transcript partially undergoes nonsense-mediated mRNA decay and is present at 43% of the normal transcript level in the fibroblasts of a healthy carrier. CONCLUSION: Previously heterozygous SALL1 mutations and deletions have been associated with dominantly inherited anal-renal-radial-ear developmental anomalies. We identified an allelic recessive SALL1-related MCA-MR. Our findings imply that quantity and quality of SALL1 transcript are important for SALL1 function and determine phenotype, and mode of inheritance, of allelic SALL1-related disorders. This novel MCA-MR emphasizes SALL1 function as critical for normal central nervous system development and warrants a detailed neurologic investigation in all individuals with SALL1 mutations.

Publication status:: Published

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APA Style

Vodopiutz, J., Zoller, H., Fenwick, A., Arnhold, R., Schmid, M., Prayer, D., Müller, T., Repa, A., Pollak, A., Aufricht, C., Wilkie, A., & Janecke, A. (2013). Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome. Journal of Pediatrics, 162(3), 612–617.

MLA Style

Vodopiutz, J, et al. “Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly-Mental Retardation Syndrome.” Journal of Pediatrics, vol. 162, no. 3, 2013, pp. 612–17.

Chicago Style

Vodopiutz, J, H Zoller, A Fenwick, et al. 2013. “Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly-Mental Retardation Syndrome.” Journal of Pediatrics 162 (3): 612–17.
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