PMC8680350_01
(A)Three generations of pedigree of family. (B) Anterior, lateral photographs and radiographs of sibling 1 that demonstrate platyspondyly with thinning of the vertebral bodies and secondary kyphosis. (C) Photographs of sibling 2 showing the main clinical features.
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F1
The instrumental examinations revealed platyspondyly with thinning of the vertebral bodies due to osteoporosis and thoracic deformity with secondary kyphosis and bilateral posterior subcapsular cataract and hearing loss (Figure 1B). In addition, the baby presented right cryptorchidism (Figure 1C).
Workflow diagram of variants' filtering in patient-parents trio exome.
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F2
CADD_phreed >=25 (applied only to missense variants), frequency <1% or not reported were filtered. Considering the parental consanguinity, we decided to focus our attention on variants lying in disease genes consistent with autosomal recessive mode of inheritance (Figure 2).
(A) Variant confirmation and segregation analysis by Sanger sequencing. (B) Schematic view of the XYLT2 protein (NM_022167), showing previously reported variants and the novel variant identified in this study (in box). Different types of variants are labeled with different colors.
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F3
In sibling 2, Sanger sequencing revealed the same mutation in the XYLT2 gene in homozygous state (Figure 3A).