Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome.
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2013
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| _version_ | 1826258012717711360 |
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| author | Vodopiutz, J Zoller, H Fenwick, A Arnhold, R Schmid, M Prayer, D Müller, T Repa, A Pollak, A Aufricht, C Wilkie, A Janecke, A |
| author_facet | Vodopiutz, J Zoller, H Fenwick, A Arnhold, R Schmid, M Prayer, D Müller, T Repa, A Pollak, A Aufricht, C Wilkie, A Janecke, A |
| author_sort | Vodopiutz, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:27:17Z |
| format | Journal article |
| id | oxford-uuid:086bec9c-286c-491e-8a2d-650a748dc424 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:27:17Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:086bec9c-286c-491e-8a2d-650a748dc4242022-03-26T09:12:47ZHomozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:086bec9c-286c-491e-8a2d-650a748dc424EnglishSymplectic Elements at Oxford2013Vodopiutz, JZoller, HFenwick, AArnhold, RSchmid, MPrayer, DMüller, TRepa, APollak, AAufricht, CWilkie, AJanecke, A 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. |
| spellingShingle | Vodopiutz, J Zoller, H Fenwick, A Arnhold, R Schmid, M Prayer, D Müller, T Repa, A Pollak, A Aufricht, C Wilkie, A Janecke, A Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome. |
| title | Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome. |
| title_full | Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome. |
| title_fullStr | Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome. |
| title_full_unstemmed | Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome. |
| title_short | Homozygous SALL1 mutation causes a novel multiple congenital anomaly-mental retardation syndrome. |
| title_sort | homozygous sall1 mutation causes a novel multiple congenital anomaly mental retardation syndrome |
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