Sub-Exome Target Sequencing in a Family With Syndactyly Type IV Due to a Novel Partial Duplication of the LMBR1 Gene: First Case Report in Fujian Province of China

Shi, Lijing; Huang, Hui; Jiang, Qiuxia; Huang, Rongsen; Fu, Wanyu; Mao, Liangwei; Wei, Xiaoming; Cui, Huanhuan; Lin, Keke; Cai, Licheng; Yang, You; Wang, Yuanbai; Wu, Jing

doi:10.3389/fgene.2020.00130

Cited by 5 publications

(3 citation statements)

References 27 publications

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“…Likewise, the duplication of 115.3 kb at a locus called ZRS (limb-specific cis regulator on chromosome 7 has been linked with SD4 [22][23][24][25]. Recently, in two different studies large duplications that involve several exons in the LMBR1, present on the same locus a chromosome 7, were associated with SD4 deformity in two large Chinese families [50,51] A missense mutation (c.950A>G;p.Q317R) in the HOXD13 has been confirmed to cause SD5 in a large Chinese family [27].…”

Section: Genetic Factors Underlying the Differential Phenotypes Of Sy...mentioning

confidence: 99%

Recent Advances in Syndactyly: Basis, Current Status and Future Perspectives

Zaib

Rashid

Khan

et al. 2022

Genes

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A comprehensive summary of recent knowledge in syndactyly (SD) is important for understanding the genetic etiology of SD and disease management. Thus, this review article provides background information on SD, as well as insights into phenotypic and genetic heterogeneity, newly identified gene mutations in various SD types, the role of HOXD13 in limb deformities, and recently introduced modern surgical techniques for SD. This article also proposes a procedure for genetic analysis to obtain a clearer genotype–phenotype correlation for SD in the future. We briefly describe the classification of non-syndromic SD based on variable phenotypes to explain different phenotypic features and mutations in the various genes responsible for the pathogenesis of different types of SD. We describe how different types of mutation in HOXD13 cause various types of SD, and how a mutation in HOXD13 could affect its interaction with other genes, which may be one of the reasons behind the differential phenotypes and incomplete penetrance. Furthermore, we also discuss some recently introduced modern surgical techniques, such as free skin grafting, improved flap techniques, and dermal fat grafting in combination with the Z-method incision, which have been successfully practiced clinically with no post-operative complications.

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Section: Genetic Factors Underlying the Differential Phenotypes Of Sy...mentioning

confidence: 99%

Recent Advances in Syndactyly: Basis, Current Status and Future Perspectives

Zaib

Rashid

Khan

et al. 2022

Genes

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“…Syndactyly is a variable manifestation [ 26 , 28 , 42 ] GLI3 Pallister–Hall syndrome 146510 Haploinsufficiency, c.1468_1469insG and c.1007_1008dupAC AD Hypothalamic hamartoma, pituitary dysfunction, central polydactyly, and variable degree of syndactyly BMP suppression [ 30 , 43 , 44 ] Greig cephalopolysyndactyly syndrome 175700 c.2374C > T; p.Arg792* AD Frontal bossing, scaphocephaly, and hypertelorism associated with pre- and postaxial polydactyly and variable syndactyly LMBR1 Triphalangeal thumb-polysyndactyly syndrome 174500 Position 287 on ZRS enhancer AD Thumb in this malformation is usually opposable and possesses a normal metacarpal. Variable degree of syndactyly [ 31 , 32 , 45 ] DHCR7 Smith–Lemli–Opitz syndrome 270400 c.453G > A; p.W151X AR Affects multiple body systems with Syndactyly of toes 2 and 3 being a common finding [ 33 , 46 ] RAB23 Carpenter syndrome 201000 Homozygous nonsense/frameshift pathogenic variants c.434 T > A; p.L145X AR Craniosynostosis, polysyndactyly, obesity, and cardiac defects [ 39 , 47 – 49 ] ...…”

Section: Syndromic Syndactyly Genetic Determinantsmentioning

confidence: 99%

“…Most GLI3 gene variants are associated with haploinsufficiency of the GLI3 gene, which eventually cause the skewing of GLI3 Activator (GLIA) or Repressor (GLIR) formation [ 30 ]. Common genetic determinant for TPS includes duplications spanning the LMBR1 gene [ 7 , 31 , 32 ], and the RAB23 gene (6p12.1-q12), encodes a negative regulator of the signaling in sonic hedgehog (SHH), perturbed in Carpenters syndrome. As for SLOS, the gene encoding the enzyme 7-dehydrocholesterol (7-DHC) reductase ( DHCR7 : 11q13.4), is known to be deregulated.…”

Section: Syndromic Syndactyly Genetic Determinantsmentioning

confidence: 99%

Genetic determinants of syndactyly: perspectives on pathogenesis and diagnosis

Cassim

Hettiarachchi

Dissanayake

2022

Orphanet J Rare Dis

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The formation of the digits is a tightly regulated process. During embryogenesis, disturbance of genetic pathways in limb development could result in syndactyly; a common congenital malformation consisting of webbing in adjacent digits. Currently, there is a paucity of knowledge regarding the exact developmental mechanism leading to this condition. The best studied canonical interactions of Wingless‐type–Bone Morphogenic Protein–Fibroblast Growth Factor (WNT–BMP–FGF8), plays a role in the interdigital cell death (ICD) which is thought to be repressed in human syndactyly. Animal studies have displayed other pathways such as the Notch signaling, metalloprotease and non-canonical WNT-Planar cell polarity (PCP), to also contribute to failure of ICD, although less prominence has been given. The current diagnosis is based on a clinical evaluation followed by radiography when indicated, and surgical release of digits at 6 months of age is recommended. This review discusses the interactions repressing ICD in syndactyly, and characterizes genes associated with non-syndromic and selected syndromes involving syndactyly, according to the best studied canonical WNT-BMP-FGF interactions in humans. Additionally, the controversies regarding the current syndactyly classification and the effect of non-coding elements are evaluated, which to our knowledge has not been previously highlighted. The aim of the review is to better understand the developmental process leading to this condition.

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