Identification of Novel Risk Variants of Non-Syndromic Cleft Palate by Targeted Gene Panel Sequencing

被引：3

作者：

Dabrowska, Justyna ^{[1
]}

Biedziak, Barbara ^{[2
]}

Bogdanowicz, Agnieszka ^{[2
]}

Mostowska, Adrianna ^{[1
]}

机构：

[1] Poznan Univ Med Sci, Dept Biochem & Mol Biol, 6 Swiecickiego St, PL-60781 Poznan, Poland

[2] Poznan Univ Med Sci, Dept Orthodont & Craniofacial Anomalies, PL-60812 Poznan, Poland

来源：

JOURNAL OF CLINICAL MEDICINE | 2023年 / 12卷 / 05期

关键词：

non-syndromic cleft palate; rare coding variants; pathogenic variants; NGS gene panel; GENOME-WIDE ASSOCIATION; NANCE-HORAN-SYNDROME; CANDIDATE GENES; OROFACIAL CLEFTS; WNT GENES; RARE VARIANTS; LIP; MUTATIONS; IRF6; DIFFERENTIATION;

D O I：

10.3390/jcm12052051

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Non-syndromic cleft palate (ns-CP) has a genetically heterogeneous aetiology. Numerous studies have suggested a crucial role of rare coding variants in characterizing the unrevealed component of genetic variation in ns-CP called the "missing heritability". Therefore, this study aimed to detect low-frequency variants that are implicated in ns-CP aetiology in the Polish population. For this purpose, coding regions of 423 genes associated with orofacial cleft anomalies and/or involved with facial development were screened in 38 ns-CP patients using the next-generation sequencing technology. After multistage selection and prioritisation, eight novel and four known rare variants that may influence an individual's risk of ns-CP were identified. Among detected alternations, seven were located in novel candidate genes for ns-CP, including COL17A1 (c.2435-1G>A), DLG1 (c.1586G>C, p.Glu562Asp), NHS (c.568G>C, p.Val190Leu-de novo variant), NOTCH2 (c.1997A>G, p.Tyr666Cys), TBX18 (c.647A>T, p.His225Leu), VAX1 (c.400G>A, p.Ala134Thr) and WNT5B (c.716G>T, p.Arg239Leu). The remaining risk variants were identified within genes previously linked to ns-CP, confirming their contribution to this anomaly. This list included ARHGAP29 (c.1706G>A, p.Arg569Gln), FLNB (c.3605A>G, Tyr1202Cys), IRF6 (224A>G, p.Asp75Gly-de novo variant), LRP6 (c.481C>A, p.Pro161Thr) and TP63 (c.353A>T, p.Asn118Ile). In summary, this study provides further insights into the genetic components contributing to ns-CP aetiology and identifies novel susceptibility genes for this craniofacial anomaly.

引用

页数：13

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