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Case Reports
. 2023 Apr;191(4):1083-1088.
doi: 10.1002/ajmg.a.63101. Epub 2023 Jan 3.

Concurrent de novo ZFHX4 variant and 16q24.1 deletion in a patient with orofacial clefting; a potential role of ZFHX4 and USP10

Marijn Créton  1 , Frank Wagener  1   2 , Maarten Massink  3 , Willem Fennis  4 , Marjon Bloemen  1   2 , Jan Schols  1 , Miranda Aarts  1 , Aebele Mink van der Molen  5 , Gijs van Haaften  3 , Marie José van den Boogaard  3
Affiliations
Case Reports

Concurrent de novo ZFHX4 variant and 16q24.1 deletion in a patient with orofacial clefting; a potential role of ZFHX4 and USP10

Marijn Créton et al. Am J Med Genet A. 2023 Apr.

Abstract

A girl with a unilateral cleft lip, alveolus and palate, tooth agenesis, and mild dysmorphic features, without a specific underlying syndrome diagnosis, was genotypically characterized and phenotypically described. Cleft gene panel analysis, single-nucleotide polymorphism (SNP) array, whole genome sequencing (WGS), whole exome sequencing, and quantitative PCR (Q-PCR) analysis were used as diagnostic tests. SNP array revealed a maternal deletion at 16q24.1, encompassing the cleft candidate gene USP10. WES revealed an additional de novo Loss-of-Function variant (p.(Asn838fs)) in the Zinc-Finger-Homeobox-4 (ZFHX4) gene. Q-PCR was performed to explore the effect of the ZFHX4 variant and the deletion in 16q24.1. The mRNA expression of a selection of putative target genes involved in orofacial clefting showed a lowered expression of USP10 (52%), CRISPLD2 (31%), and CRISPLD1 (1%) compared to the control. IRF6 showed no difference in gene expression. This case supports ZFHX4 as a novel cleft gene and suggests USP10 may contribute to the etiology of orofacial clefts in humans.

Keywords: CRISPLD1; CRISPLD2; IRF6; USP10; ZFHX4; cleft palate.

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Comment in

  • ZFHX4 truncating variant and orofacial clefting.
    Sorrentino U, Fedrigo M, Calò AP, Perin M, Veronese P, Salviati L. Sorrentino U, et al. Am J Med Genet A. 2024 Jan;194(1):115-116. doi: 10.1002/ajmg.a.63353. Epub 2023 Jul 11. Am J Med Genet A. 2024. PMID: 37434517 No abstract available.

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