Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type IC and a review of the relate
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CASE REPORT
Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type IC and a review of the related literature Qiang Zhang* , Zailong Qin, Shang Yi, Hao Wei, Xun Zhao Zhou and Jiasun Su
Abstract Background: Autosomal recessive cutis laxa type IC (ARCL IC, MIM: #613177) results from a mutation in the LTBP4 gene (MIM: #604710) on chromosome 19q13. Case presentation: A 28-day-old Chinese infant with generalized cutis laxa accompanied by impaired pulmonary, gastrointestinal, genitourinary, retinal hemorrhage, abnormality of coagulation and hyperbilirubinemia was admitted to our hospital. To find out the possible causes of these symptoms, whole-exome sequencing was performed on the infant. Two novel pathogenic frame-shift variants [c.605_606delGT (p.Ser204fs * 8) and c.1719delC (p.Arg574fs * 199)] of the LTBP4 gene associated with ARCL IC were found which was later verified by Sanger sequencing. The pathogenicity of mutations was subsequently assessed by several software programs and databases. In addition, an analytical review on the clinical phenotypes of the disease previously reported in literature was performed. Conclusions: This is the first report of a Chinese infant with ARCL IC in China due to novel pathogenic variations of LTBP4. Our study extends the cutis laxa type IC mutation spectrum as well as the phenotypes associated with the disease in different populations. Keywords: ARCL IC, LTBP4 gene, Mutation Background Cutis laxa, a disease with clinical heterogeneity, is characterized by inelastic and loose skin and it may present systemic manifestations of variable severity [1]. Autosomal recessive cutis laxa (ARCL) is comprise of three subtypes: ARCL I, (ARCL IA, ARCL IB and ARCL IC), and ARCL II (ARCL II A, ARCL IIB, ARCL IIC, ARCL ID and ARCL III [2]. Previous studies have revealed that LTBPS is related to ARCL IC in the gene encoding process [3]. To date, only twenty-four LTBP4 variations have been recorded in a total of 20 sufferers. Herein, we uncovered
*Correspondence: [email protected] Laboratory of Genetic and Metabolism, Department of Paediatric Endocrine and Metabolism, Maternal and Child Health Hospital of Guangxi, Nanning 530000, China
two pathogenic variations in LTBP4 by whole-exome sequencing (WES). LTBP4 is a key gene related to the formation of the microfibrillar structures [4]. Transforming growth factor beta (TGFβ) is secreted into the extracellular matrix as a tightly bound dimeric pro-peptide referred to as latencyassociated peptide. This is the small latent complex, which then binds to LTBP4, to form a large latent complex. This process ensures that TGFβmolecules become a part of the microfiber system, from which the releasing process is managed by different mechanisms. Because of this, LTBP4 has a crucial function in the regulation of TGFβ1 signaling [5, 6]. We were able to confirm that a Chinese newborn had signs of ARCL1 and summarized the characteristics of this individual as well as other patients with LTPB 4 related to cutis laxa
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