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Case Reports
. 2021 Apr 5;12(4):528.
doi: 10.3390/genes12040528.

"VSports" Intragenic Deletions in FLNB Are Part of the Mutational Spectrum Causing Spondylocarpotarsal Synostosis Syndrome

Kaya Fukushima  1 , Padmini Parthasarathy  1 , Emma M Wade  1 , Tim Morgan  1 , Kalpana Gowrishankar  2 , David M Markie  3 , Stephen P Robertson  1
Affiliations
Case Reports

Intragenic Deletions in FLNB Are Part of the Mutational Spectrum Causing Spondylocarpotarsal Synostosis Syndrome (V体育官网)

Kaya Fukushima et al. Genes (Basel). .

Abstract

Spondylocarpotarsal synostosis syndrome (SCT) is characterized by vertebral fusions, a disproportionately short stature, and synostosis of carpal and tarsal bones. Pathogenic variants in FLNB, MYH3, and possibly in RFLNA, have been reported to be responsible for this condition. Here, we present two unrelated individuals presenting with features typical of SCT in which Sanger sequencing combined with whole genome sequencing identified novel, homozygous intragenic deletions in FLNB (c. 1346-1372_1941+389del and c. 3127-353_4223-1836del). Both deletions remove several consecutive exons and are predicted to result in a frameshift. To our knowledge, this is the first time that large structural variants in FLNB have been reported in SCT, and thus our findings add to the classes of variation that can lead to this disorder. These cases highlight the need for copy number sensitive methods to be utilized in order to be comprehensive in the search for a molecular diagnosis in individuals with a clinical diagnosis of SCT VSports手机版. .

Keywords: FLNB; SCT; filamin B; spondylocarpotarsal synostosis syndrome. V体育安卓版.

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Conflict of interest statement (VSports手机版)

The authors declare no conflict of interest.

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Figure 1
Figure 1
Radiographs and sequence data from families A and B. (a) Spine X-ray of proband A at age 6 showing fusions of T3–T11 vertebrae and significant scoliosis. (b) IGV plot showing the novel homozygous deletion in proband A that removes exons 9–12 of FLNB. The positions of the primers used for the allele-specific PCR are indicated underneath. (c) Pedigree of family A. (d) PCR results from family A demonstrates the absence of the wild-type (WT) allele and the presence of the deletion-containing allele (Mut) in the proband (II-1) while the parents (I-1, I-2) have both WT and Mut alleles. (e) X-rays of proband B at age 9 showing fusions of T6–T9 vertebrae and capitate–hamate fusion bilaterally. (f) IGV plot showing the novel homozygous deletion in proband B that removes exons 21-24 of FLNB. The positions of the primers used for the allele-specific PCR are indicated underneath. (g) Pedigree of family B. (h) PCR results from family B showing the absence of the WT allele and the presence of the deletion-containing allele in the proband (III-1), while both alleles are found in the father (II-1) and the maternal grandmother (I-2).
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References

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