Case Report: Prenatal Diagnosis of Postaxial Polydactyly With Bi-Allelic Variants in Smoothened (SMO)

Fan, Lihong; Jin, Pengzhen; Qian, Yeqing; Shen, Guosong; Shen, Xueping; Dong, Minyue

doi:10.3389/fgene.2022.887082

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…The DNA was amplified using the following procedure: 95°C for 10 min; 35 cycles at 95°C for 30 s, 60°C for 30 s, 72°C for 30 s; 72°C for 10 min. Sequencing was performed by an ABI 3130 DNA analyzer ( 10 ).…”

Section: Methodsmentioning

confidence: 99%

Novel homozygous silent mutation of ITGB3 gene caused Glanzmann thrombasthenia

Wang

Sun

et al. 2023

Front. Pediatr.

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Glanzmann thrombasthenia (GT) is a rare inherited disease characterized by mucocutaneous bleeding due to the abnormalities in quantity or quality of platelet membrane GP IIb (CD41) or GP IIIa (CD61). GP IIb and GP IIIa are encoded by the ITGA2B and ITGB3 genes, respectively. Herein, we described a 7-year-old Chinese boy of the consanguineous couple who was diagnosed with GT based on the typical clinical manifestations, absence of blood clot retraction and the reduced expression of CD41 and CD61 in platelets. A homozygous silent variant c.1431C > T (p. G477=) of the ITGB3 gene was identified by the Whole-exome sequencing and confirmed by Sanger sequencing. The variant was predicted to affect the splicing. RT-PCR and sequencing revealed that the variant caused a deletion of 95 base pairs and frameshift, and subsequently created a premature stop codon in exon 10 of ITGB3 (p. G477Afs*30). It was indicated that the variant c.1431C > T (p. G477=) of ITGB3 was the cause for Glanzmann thrombasthenia. Our findings expanded the mutation spectrum and provided the information for the genetic counseling, prenatal diagnosis and preimplantation genetic testing (PGT).

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Section: Methodsmentioning

confidence: 99%

Novel homozygous silent mutation of ITGB3 gene caused Glanzmann thrombasthenia

Wang

Sun

et al. 2023

Front. Pediatr.

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“…ee/). PCR products were sequenced using the ABI 3500DX and further analyzed using DNASTAR 5.0 software (Fan et al, 2022).…”

Section: Name Of the Primermentioning

confidence: 99%

Prenatal diagnosis of recurrent moderate skeletal dysplasias in lamin B receptors

Shen

Li²,

Pan³

et al. 2023

Front. Genet.

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The lamin B receptor (LBR) gene is located in chromosome 1q42.12 and encodes the lamin B receptor, an intracellular protein that binds to lamin B. LBR mutations are associated with a broad phenotypic spectrum ranging from non-lethal to lethal skeletal dysplasias. The typical phenotypes include the Pelger−Huet anomaly (PHA) and embryonic lethal Greenberg dysplasia (GRBGD). With the further study of this gene, other phenotypes have been found in different individuals. This retrospective study analyzed recurrent prenatal moderate skeletal dysplasias in Chinese fetuses. Nothing malformed was detected in the fetal karyotype and microarray, while the whole-exome sequencing identified a homozygous variant (NM_002296.4:c.1757G>A, NP_002287.2:p.Arg586His) in exon 14 of the LBR gene in both fetuses. Mutation analysis in the parents confirmed that the c.1757G>A variation is heterozygous by Sanger sequencing. Intensive analysis on bioinformatics and familial co-segregation suggest that the homozygous variation in the LBR gene is responsible for this recurrent prenatal moderate skeletal dysplasia. Moreover, moderate skeletal dysplasias differ from typical GRBGD phenotypes. Our findings are based on the DNA base test and the prenatal diagnosis of skeletal dysplasia, which can be helpful in proper phenotyping and contribute to a better understanding of the correlation between the phenotype and genotype.

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A Novel Variant in the Cyto-Tail of SMO Gene Underlying Isolated Postaxial Polydactyly

Javed Khan,

Abdullah,

Khan

et al. 2024

Mol Syndromol

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Background: Polydactyly is one of the most common hereditary limb malformations, characterized by presence of additional digits in hands and/or feet. It is present either in isolated form or in combination with other features. Preaxial polydactyly with extra digit on the outside of the thumb or big toe, and postaxial polydactyly with extra digit on the outside of the little finger or little toe are the two main forms of polydactyly. Methods and Results: In the present study, two unrelated consanguineous families segregating PAP in an autosomal recessive manner were investigated. Whole exome sequencing, followed by segregation analysis using Sanger sequencing, revealed a homozygous missense variant [c.1792 G>A; p.(Gly598Arg); NM_005631.5] in the SMO in both families. Proteins SMO, PTCH, and GLI act as major components of the Sonic hedgehog pathway, which transmits signals to embryonic cells for cellular differentiation. Homology modeling revealed that the variant in SMO may disrupt proper protein folding and interaction with other molecules. Conclusion: Our study has revealed the second direct involvement of a sequence variant in the SMO causing isolated polydactyly. This study will highlight the importance of the inclusion of the SMO gene in screening individuals presenting polydactyly in hands and feet.

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Case Report: Prenatal Diagnosis of Postaxial Polydactyly With Bi-Allelic Variants in Smoothened (SMO)

Cited by 3 publications

References 34 publications

Novel homozygous silent mutation of ITGB3 gene caused Glanzmann thrombasthenia

Novel homozygous silent mutation of ITGB3 gene caused Glanzmann thrombasthenia

Prenatal diagnosis of recurrent moderate skeletal dysplasias in lamin B receptors

A Novel Variant in the Cyto-Tail of SMO Gene Underlying Isolated Postaxial Polydactyly

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