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<p>Labyrinthine aplasia, type I microtia and microdontia (LAMM) syndrome, a rare autosomal recessive disease, is characterized by labyrinthine aplasia, microtia, and microdontia initially described in 2007 by Tekin. It is evident that the syndrome is associated with <i>FGF3</i>, and several mutations within the <i>FGF3</i> gene have been reported in individuals with LAMM syndrome. We have identified a novel mutation (c.155C&gt;G,p.Thr52Arg) which has never been reported. Furthermore, the pathogenicity of the new mutation has not yet been tested in human or zebrafish models. We present a case of LAMM syndrome with cholesteatoma in a 5-year-old male with compound heterozygosity for <i>FGF3</i> mutations, born to non-consanguineous parents. This report describes a novel mutation (c.155C&gt;G,p.Thr52Arg) that has never been previously reported and (c.310C&gt;T,p.Arg104Ter) that have been reported several times. We tested its pathogenicity by (1) detecting the stable inheritance of gene mutations of <i>FGF3</i> (c.155C&gt;G,p.Thr52Arg) in DNA, 3D domain, and species conservation and (2) injecting mRNA into zebrafish to observe potential anomalies. The novel case showed the presence of cholesteatoma that may expand the manifestation of LAMM syndrome. There were no mutation-related bands observed in PCR analysis for the inheritance of the mutation sites. The residue (Thr52) is evolutionarily conserved across species. Analysis of the 3D structure indicated variations in FGF3’s structural surface, possibly associated with illness etiology. Injection of constructed mutant plasmid into zebrafish resulted in evident malformation. The present case is the first documented report of LAMM syndrome accompanied by cholesteatoma, unveiling a novel possible pathogenic mutation of <i>FGF3.</i> The presence of otitis media and cholesteatoma will expand the manifestations of LAMM syndrome. The novel mutation <i>FGF3</i> (c.155C&gt;G,p.Thr52Arg) may be pathogenic by disturbing the connection of ligand of <i>FGF3</i> and receptor of <i>FGFR3</i> in the ear during fetal.</p> Graphical Abstract <p></p>

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A Novel Missense Mutation in the FGF3 Gene of a Chinese Patient with LAMM Syndrome

  • 期刊论文

  • 发表日期：

    2025年8月5日

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  • Kangjia Zhang,
  • Yong Zhang,
  • Weijing Wu,
  • Shu Yang,
  • Huaping Xie,
  • Jiaxin Liang,
  • Xiaoying Zheng,
  • Ruosha Lai

摘要

Labyrinthine aplasia, type I microtia and microdontia (LAMM) syndrome, a rare autosomal recessive disease, is characterized by labyrinthine aplasia, microtia, and microdontia initially described in 2007 by Tekin. It is evident that the syndrome is associated with FGF3, and several mutations within the FGF3 gene have been reported in individuals with LAMM syndrome. We have identified a novel mutation (c.155C>G,p.Thr52Arg) which has never been reported. Furthermore, the pathogenicity of the new mutation has not yet been tested in human or zebrafish models. We present a case of LAMM syndrome with cholesteatoma in a 5-year-old male with compound heterozygosity for FGF3 mutations, born to non-consanguineous parents. This report describes a novel mutation (c.155C>G,p.Thr52Arg) that has never been previously reported and (c.310C>T,p.Arg104Ter) that have been reported several times. We tested its pathogenicity by (1) detecting the stable inheritance of gene mutations of FGF3 (c.155C>G,p.Thr52Arg) in DNA, 3D domain, and species conservation and (2) injecting mRNA into zebrafish to observe potential anomalies. The novel case showed the presence of cholesteatoma that may expand the manifestation of LAMM syndrome. There were no mutation-related bands observed in PCR analysis for the inheritance of the mutation sites. The residue (Thr52) is evolutionarily conserved across species. Analysis of the 3D structure indicated variations in FGF3’s structural surface, possibly associated with illness etiology. Injection of constructed mutant plasmid into zebrafish resulted in evident malformation. The present case is the first documented report of LAMM syndrome accompanied by cholesteatoma, unveiling a novel possible pathogenic mutation of FGF3. The presence of otitis media and cholesteatoma will expand the manifestations of LAMM syndrome. The novel mutation FGF3 (c.155C>G,p.Thr52Arg) may be pathogenic by disturbing the connection of ligand of FGF3 and receptor of FGFR3 in the ear during fetal.

Graphical Abstract