The CRISPLD2 gene is involved in cleft lip and/or cleft palate in a Chinese population

Shi, Xi; Liu, Ruimin; Yang, Liang; Wu, Hua; Li, Peiqiang; Liang, Yuanxue; Xie, Xiaodong; Yao, Ting; Zhang, Tingting; Yu, Min

doi:10.1002/bdra.20840

Cited by 22 publications

(32 citation statements)

References 36 publications

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“…There are however intriguing associations between the paralogue, CRISPLD2 and non-syndromic cleft lip with or without cleft palate Chiquet et al, 2007;Letra et al, 2011;Shen et al, 2011;Shi et al, 2010). We found that CRISPLD2 was enriched in the normal frontonasal mass (3.0 fold) which expands the limited expression analysis presented in the original study (Chiquet et al, 2007).…”

Section: Pi15 and The Relationship To Orofacial Cleftingsupporting

confidence: 67%

Identification and functional analysis of novel facial patterning genes in the duplicated beak chicken embryo

Nimmagadda

Buchtová

et al. 2015

Developmental Biology

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Cranial neural crest cells form the majority of the facial skeleton. However exactly when the pattering information and hence jaw identity is established is not clear. We know that premigratory neural crest cells contain a limited amount of information about the lower jaw but the upper jaw and facial midline are specified later by local tissue interactions. The environmental signals leading to frontonasal identity have been explored by our group in the past. Altering the levels of two signaling pathways (Bone Morphogenetic Protein) and retinoic acid (RA) in the chicken embryo creates a duplicated midline on the side of the upper beak complete with egg tooth in place of maxillary derivatives (Lee et al., 2001). Here we analyze the transcriptome 16 h after bead placement in order to identify potential mediators of the identity change in the maxillary prominence. The gene list included RA, BMP and WNT signaling pathway genes as well as transcription factors expressed in craniofacial development. There was also cross talk between Noggin and RA such that Noggin activated the RA pathway. We also observed expression changes in several poorly characterized genes including the upregulation of Peptidase Inhibitor-15 (PI15). We tested the functional effects of PI15 overexpression with a retroviral misexpression strategy. PI15 virus induced a cleft beak analogous to human cleft lip. We next asked whether PI15 effects were mediated by changes in expression of major clefting genes and genes in the retinoid signaling pathway. Expression of TP63, TBX22, BMP4 and FOXE1, all human clefting genes, were upregulated. In addition, ALDH1A2, ALDH1A3 and RA target, RARβ were increased while the degradation enzyme CYP26A1 was decreased. Together these changes were consistent with activation of the RA pathway. Furthermore, PI15 retrovirus injected into the face was able to replace RA and synergize with Noggin to induce beak transformations. We conclude that the microarrays have generated a rich dataset containing genes with important roles in facial morphogenesis. Moreover, one of these facial genes, PI15 is a putative clefting gene and is in a positive feedback loop with RA.

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Section: Pi15 and The Relationship To Orofacial Cleftingsupporting

confidence: 67%

Identification and functional analysis of novel facial patterning genes in the duplicated beak chicken embryo

Nimmagadda

Buchtová

et al. 2015

Developmental Biology

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“…Interestingly, a recent report showed a decreasing risk of facial clefts in individuals with same SNP genotype among Han Chinese population [15]. In agreement with our study, Shen et al also found significant difference in genotype and allele frequencies of rs1546124 (OR = 2.30; 95%, CI = 1.58-3.34; P < 0.001) in nsCL/P patients compared with controls [6]. In contrast, a family-based study from Italian population revealed no association between rs1546124 allele or genotype and ns/CLP [8].…”

Section: Discussionsupporting

confidence: 92%

“…In the present study, 18 CRISPLD2 SNPs were evaluated in 380 individuals. Our case-control study showed evidence for association between the CRISPLD2 gene and ns/CLP in this Xinjiang Uyghur population, providing further support to the previous findings of Chiquet et al [5], Shen et al [6], and Shi et al [20] that CRISPLD2 is involved in the pathogenesis of ns/CLP. The locus rs1546124, one of the most investigated markers of the CRISPLD2 gene is located in exon2, 51 bp upstream of the ATG start codon.…”

Section: Discussionsupporting

confidence: 90%

“…Besides, Yuan et al [19] found significant role of CRISPLD2 gene in the development of the zebrafish craniofacies and alteration of normal protein levels. Despite the significance of CRISPLD2 gene in the development of nsCL/P, only seven association and linkage studies have been undertaken to verify the potential association between functional polymorphisms of CRISPLD2 gene and an increased risk of nsCL/P [5][6][7][8][9]20,21] since Chiquet et al originally reported the association between the CRISPLD2 gene and nsCLP [5].…”

Section: Discussionmentioning

confidence: 99%

“…In a linkage disequilibrium (LD) analysis, Chiquet et al found significant association of CRISPLD2 with both Hispanic and white nsCL/P cohorts [5]. A more recent study from China showed that the CRISPLD2 gene contributes to the etiology of nsCL/P in the Northwestern Chinese population [6]. However, other association studies yielded conflicting results in different populations [7][8][9].…”

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confidence: 99%

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Preliminary evidence of an interaction between the CRISPLD2 gene and non-syndromic cleft lip with or without cleft palate (nsCL/P) in Xinjiang Uyghur population, China

Mijiti

Wang

Maimaiti

et al. 2015

International Journal of Pediatric Otorhinolaryngology

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

Créton

Wagener

Massink

et al. 2023

American J of Med Genetics Pt A

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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.

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The CRISPLD2 gene is involved in cleft lip and/or cleft palate in a Chinese population

Abstract: Our results suggest that the CRISPLD2 gene contributes to the etiology of NSCLP in the Northwestern Chinese population. SNP rs1546124 is significantly related to NSCLP, associated with both CL/P and CPO groups, and SNP rs4783099 is significantly associated with CPO.

Cited by 22 publications

References 36 publications

Identification and functional analysis of novel facial patterning genes in the duplicated beak chicken embryo

Identification and functional analysis of novel facial patterning genes in the duplicated beak chicken embryo

Preliminary evidence of an interaction between the CRISPLD2 gene and non-syndromic cleft lip with or without cleft palate (nsCL/P) in Xinjiang Uyghur population, China

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

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