Townes-Brocks syndrome with craniosynostosis in two siblings |
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| Affiliation: | 1. Neonatology Unit, Mother-Child Department, University Hospital of Modena, Italy;2. Pediatric Surgery Unit, Mother-Child Department, University Hospital of Modena, Italy;3. Genetic Unit, University Hospital of Modena, Italy;4. PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Italy;5. Postgraduate School of Pediatrics, Department of Medical and Surgical Sciences for Mother, Children and Adults, University of Modena and Reggio Emilia, Italy;6. Pediatric Unit, Mother-Child Department, University Hospital of Modena, Italy;1. First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China;2. Medical College of Pediatrics, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China;1. Department of Neurology, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium;2. Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium;3. Center for Medical Genetics, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium;1. Hacettepe University Faculty of Medicine, Department of Pediatric Genetics, Ankara, Turkey;2. Hacettepe University Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey;3. Hacettepe University Faculty of Medicine, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Ankara, Turkey;4. Hacettepe University Faculty of Medicine, Department of Pediatrics, Division Pediatric and Perinatal Pathology, Ankara, Turkey;1. Biochemical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Egypt;2. Oro-dental Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt;3. Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt |
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| Abstract: | This report describes a novel truncating c.709C > T p.(Gln237*) SALL1 variant in two siblings exhibiting sagittal craniosynostosis as a unique feature of Townes-Brocks syndrome (TBS, OMIM #107480). TBS is a rare autosomal dominant syndrome with variable phenotypes, including anorectal, renal, limb, and ear abnormalities, which results from heterozygous variants in the SALL1 gene, predominantly located in the 802 bp “hot spot region” within exon 2. Recent studies have suggested that aberrations in primary cilia and sonic hedgehog signalling contribute to the TBS phenotypes. The presence of the novel c.709C > T p.(Gln237*) SALL1 variant was confirmed in both the siblings and their father, whereas no mutations currently associated with craniosynostosis were detected. We hypothesise that the truncating c.709C > T p.(Gln237*) SALL1 variant, which occurs outside the “hot spot region” and inside the glutamine-rich domain coding region, could interfere with ciliary signalling and mechanotransduction, contributing to premature fusion of calvarial sutures. This report broadens the genetic and phenotypic spectrum of TBS and provides the first clinical evidence of craniosynostosis as a novel feature of the syndrome. |
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| Keywords: | Townes-Brocks syndrome Craniosynostosis Ciliopathies |
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