Abstract
Spondyloocular syndrome (SOS) is a skeletal disorder caused by pathogenic variants in XYLT2 gene encoding a xylotransferase involved in the biosynthesis of proteoglycans. This condition, with autosomal recessive inheritance, has a high phenotypic variability. It is characterized by bone abnormalities (osteoporosis, fractures), eye and cardiac defects, hearing impairment, and varying degrees of developmental delay. Until now only 20 mutated individuals have been reported worldwide. Here, we describe two siblings from consanguineous healthy parents in which a novel homozygous frameshift variant c.1586dup p(Thr530Hisfs*) in the XYLT2 gene was detected by exome sequencing (ES). The first patient (9 years) presented short stature with skeletal defects, long face, hearing loss and cataract. The second patient, evaluated at a few days of life, showed macrosomia, diffuse hypertrichosis on the back, overabundant skin in the retronucal area, flattened facial profile with drooping cheeks, elongated eyelid rims, wide and flattened nasal bridge and turned down corners of the mouth. During the prenatal period, high nuchal translucency and intestinal hyperechogenicity were observed at ultrasound. In conclusion, these two siblings with a novel pathogenic variant in XYLT2 further expand the clinical and mutational spectrum of SOS.
Highlights
Spondyloocular syndrome (SOS) (OMIM #605822) is a very rare autosomal recessive skeletal disorder caused by pathogenic variants in XYLT2 gene located on chromosome 17q21 (Umair et al, 2018)
The baby showed hypovalid suction and poor growth. She had speech and psychomotor delay: she crawled at 5 years old, she was able to walk at 6 years old, she acquired sphincter control at 6 years old
We described two additional patients with SOS and reported one novel homozygous variant, a frameshift deletion in the XYLT2 gene c.1586dup p.(Thr530Hisfs*16)
Summary
Spondyloocular syndrome (SOS) (OMIM #605822) is a very rare autosomal recessive skeletal disorder caused by pathogenic variants in XYLT2 gene located on chromosome 17q21 (Umair et al, 2018). The XYLT2 gene encodes a xylosyltransferase II, which catalyzes the initial phase of proteoglycans (PGs) assembly. PGs are found on the cell surface, in secretory granules and in the extracellular matrix. PGs are essential for many physiological processes, such as signal transduction, cellular homeostasis, membrane integrity, corepressor activity, Novel Pathogenic Variant in XYLT2. PGs consist of a core protein, which is linked to glycosaminoglycan (GAG) disaccharide chains. Of GAGs on the core protein results in different groups of sulfated PGs such as chondroitin sulfate (CSPGs), heparan sulfate (HSPGs) and modified form of CSPGs, the dermatan sulfate (DSPGs) (Couchman and Pataki, 2012)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
