Spondylo-ocular Syndrome Due to a Novel Variant in XYLT2 in an Omani Patient

Al‐Araimi, Musallam; Hamza, Nishath; Al-Hosni, Aliya; Maimani, Ashwaq Al

doi:10.1055/s-0040-1715113

Cited by 2 publications

(3 citation statements)

References 7 publications

(9 reference statements)

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“…When the literature was reviewed, it was discovered that 24 cases (eight females and 16 males) of SOS with a genetic diagnosis had been reported from 13 families (Al‐Araimi et al, 2022; Doddato et al, 2021; Guleray et al, 2019; Kausar et al, 2019; Munns et al, 2015; Taylan et al, 2016; Taylan et al, 2017; Umair et al, 2018). Consanguinity was determined in 10 of 13 families.…”

Section: Discussionmentioning

confidence: 99%

“…To date, four homozygous frameshift deletions, one homozygous frameshift duplication, two homozygous nonsense, and six homozygous missense variants have been reported in XYLT2 (Al‐Araimi et al, 2022; Doddato et al, 2021; Guleray et al, 2019; Kausar et al, 2019; Munns et al, 2015; Taylan et al, 2016; Taylan et al, 2017; Umair et al, 2018). The genotype–phenotype relationship is unknown, but frameshift and nonsense pathogenic variants have been associated with a more severe phenotype than missense pathogenic variants (Taylan & Mäkitie, 2016).…”

Section: Discussionmentioning

confidence: 99%

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Bisphosphonate treatment at spondylo‐ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature

Büyükyılmaz

Adıgüzel

Kılıc

2023

American J of Med Genetics Pt A

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Spondylo‐ocular syndrome is a rare autosomal recessive disorder characterized by generalized osteoporosis, hearing loss, visual impairment due to cataract, and platyspondyly. Previous studies have revealed that the syndrome is caused by pathogenic variants in the XYLT2 gene. A patient with spondylo‐ocular syndrome and two heterozygous pathogenic variant in the XYLT2 gene in compound state are described here. The patient presented with osteoporosis, platyspondyly, ocular findings, hearing loss, kyphosis, scoliosis, facial findings, intellectual disability, and undescended testicles. Previous reports of bisphosphonate treatment response were variable, whereas a long‐term follow‐up with bisphosphonate treatment in this case resulted in normalization of vertebral structures. Reporting such cases helps to determine the appropriate genotype–phenotype correlation in patients with XYLT2‐related pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bisphosphonate treatment at spondylo‐ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature

Büyükyılmaz

Adıgüzel

Kılıc

2023

American J of Med Genetics Pt A

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“…Homozygous XYLT2 mutations lead to spondylo-ocular syndrome, which is associated with short stature, retinal detachment, amblyopia, nystagmus, hearing loss, heart valve defects, bone fragility and mild learning difficulties [ 18 , 19 , 20 , 21 ]. To date, 24 patients from 13 different families have been described harboring this syndrome [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Predominantly homozygous mutations lead to the clinical picture of spondylo-ocular syndrome, but the most recently discovered pathogenic mutations were compound heterozygous [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Xylosyltransferase-Deficiency in Human Dermal Fibroblasts Induces Compensatory Myofibroblast Differentiation and Long-Term ECM Reduction

Kleine,

Kühle,

et al. 2024

Biomedicines

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Desbuquois dysplasia type 2 (DBQD2) and spondylo-ocular syndrome (SOS) are autosomal recessive disorders affecting the extracellular matrix (ECM) and categorized as glycosaminoglycan (GAG) linkeropathies. Linkeropathies result from mutations within glycosyltransferases involved in the synthesis of the tetrasaccharide linker, a linker between the core protein of proteoglycan (PG) and GAG. DBQD2 and SOS are caused by the isolated mutations of the xylosyltransferase (XT) isoforms. In this work, we successfully generated XYLT1- as well as XYLT2-deficient GAG linkeropathy model systems in human dermal fibroblasts using a ribonucleoprotein-based CRISPR/Cas9-system. Furthermore, it was possible to generate a complete XYLT-knockdown. Short- and long-term XT activity deficiency led to the mutual reduction in all linker transferase-encoding genes, suggesting a potential multienzyme complex with mutual regulation. Fibroblasts compensated for ECM misregulation initially by overexpressing ECM through the TGFβ1 signaling pathway, akin to myofibroblast differentiation patterns. The long-term reduction in one XT isoform induced a stress response, reducing ECM components. The isolated XYLT1-knockout exhibited α-smooth muscle actin overexpression, possibly partially compensated by unaltered XT-II activity. XYLT2-knockout leads to the reduction in both XT isoforms and a strong stress response with indications of oxidative stress, induced senescence and apoptotic cells. In conclusion, introducing XYLT-deficiency revealed temporal and isoform-specific regulatory differences.

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Spondylo-ocular Syndrome Due to a Novel Variant in XYLT2 in an Omani Patient

Cited by 2 publications

References 7 publications

Bisphosphonate treatment at spondylo‐ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature

Bisphosphonate treatment at spondylo‐ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature

Xylosyltransferase-Deficiency in Human Dermal Fibroblasts Induces Compensatory Myofibroblast Differentiation and Long-Term ECM Reduction

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