A novel ASPH variant extends the phenotype of Shawaf‐Traboulsi syndrome

Abstract

Shawaf-Traboulsi syndrome (or Traboulsi syndrome; MIM 601552) is an infrequently reported entity characterized by a typical face (long face, large nose, convex nasal ridge, underdeveloped malae, crowded teeth, retrognathia), skeletal signs (long and slender fingers, sometimes pectus deformation and hypermobile joints), and ectopia lentis with conjunctival blebs, shallow anterior chamber and iridocorneal adhesions. The entity is caused by homozygous variants in ASPH. Here, we report on a boy with the clinical diagnosis of Shawaf-Traboulsi syndrome, in whom exome sequencing allowed identification of a novel variant in ASPH. We compare the findings in the present patient to those of earlier reported patients; furthermore add new signs for this entity.

Small-molecule active pharmaceutical ingredients of approved cancer therapeutics inhibit human aspartate/asparagine-β-hydroxylase

“… 10 The upregulation of AspH and its translocalization from the endoplasmic reticulum (ER) membrane to the cell surface in cancer cells correlates with enhanced cell motility and metastatic spread resulting in a reduced lifespan of the affected patients. 11 , 12 Studies on naturally occurring mutations of human AspH presumably resulting in inactive AspH (Traboulsi syndrome) 13 , 14 , 15 , 16 and animal models 8 , 17 , 18 suggest that AspH might affect cell motility through the notch signalling pathway. Despite the combined evidence suggesting that AspH is a promising medicinal chemistry target for the development of small-molecule-based cancer therapeutics, comparatively few AspH inhibition studies using small-molecules are reported, with most of these relying either on the use of likely non-selective 19 , 20 or partially selective 21 small-molecules or on the use of l -ascorbic acid (LAA)-derived small-molecules.…”

Genetics and genomics in Peru: Clinical and research perspective

“…These microduplications correlated to Laurin–Sandrow syndrome and Haas‐type polysyndactyly, according to the ZRS region length (Lohan et al, ). Moreover, Peruvian geneticists of INSN described unique cases of pterygium‐digital keloid dysplasia (Abarca et al, ), H syndrome (Abarca Barriga, Trubnykova, Polar Córdoba, Ramos Diaz, & Aviles, ), van der Knaap syndrome (Hamilton et al, ), and Shawaf‐Traboulsi syndrome (Abarca Barriga et al, ). Last, international collaboration permitted reports of two common genetic syndromes—that is, Noonan (Kruszka et al, ) and Williams‐Beuren (Kruszka et al, )—with clinical geneticists of the National Human Genome Research Institute of The National Institutes of Health; and with other geneticists of different sites in the globe, contributing to the worldwide clinical genetics area.…”

Diverse molecular functions of aspartate β‑hydroxylase in cancer (Review)

“…Mutations in the AspH gene can have consequences in lens instability ( 14 ). Traboulsi syndrome is an extremely rare ophthalmological disorder that is caused by homozygous variants in the AspH gene, wherein facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs are observed ( 15 – 17 ). Loss of murine hydroxylase activity is associated with increased intestinal tumor incidence and developmental defects similar to those caused by altered Notch signaling ( 18 ).…”