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Novel HOXD13 variants in syndactyly type 1b and type 1c, and a new spectrum of TP63-related disorders


Syndactyly is the most common limb defect depicting the bony and/or cutaneous fusion of digits. Syndactyly can be of various types depending on the digits involved in the fusion. To date, eight syndactyly-associated genes have been reported, of which HOXD13 and GJA1 have been explored in a few syndactyly but most of them have unknown underlying genetics. In the present study HOXD13, GJA1 and TP63 genes have been screened by resequencing in 24 unrelated sporadic cases with various syndactyly. The screening revealed two pathogenic HOXD13 variants, NM_000523:c.500 A > G [p.(Y167C)], and NM_000523:c.961 A > C [p.(T321P)] in syndactyly type 1b and type 1c, respectively. This is the first report to identify HOXD13 pathogenic variant in syndactyly type 1b and third report in syndactyly type 1c pathogenesis. Furthermore, this study also reports a TP63 pathogenic variant, NM_003722:c.953 G > A [p.(R318H)] in Ectrodactyly and Cleft lip and palate (ECLP). In conclusion, the current study expands the clinical spectrum of HOXD13 and TP63-related disorders.

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Data availability

The data that support the findings of this study are openly available in the ClinVar variant depository at, reference numbers SUB8902537, SCV000257698 and SCV000659689.


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We are grateful to the patients, family members and control volunteers for willingly participating in this study. We are grateful to Science and Engineering Research Board (SERB)-DST-Government of India, for research grant (SB/YS/LS-46/2013) to Dr A. Ali; and to CSIR-Government of India, for providing junior and senior research fellowships to Dr R. Patel. We are also grateful to Dr A. Mani, and Dr B.S. Yadav, MNNIT, Allahabad for help during in silico work and to ISLS-I.Sc.-BHU for providing their laboratory facilities.

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RP: Conducted the study, interpreting and reporting of GLI3 variants and manuscript preparation; SKS and VB: Clinical evaluation and sample collection; AA: Conceived and led the project, study design, data analysis, manuscript preparation, and supervised the study.

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Correspondence to Akhtar Ali.

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Patel, R., Singh, S.K., Bhattacharya, V. et al. Novel HOXD13 variants in syndactyly type 1b and type 1c, and a new spectrum of TP63-related disorders. J Hum Genet 67, 43–49 (2022).

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