{Reference Type}: Journal Article
{Title}: A novel heterozygous mutation in PTHLH causing autosomal dominant brachydactyly type E complicated with short stature.
{Author}: Sun J;Yang N;Xu Z;Cheng H;Zhang X;
{Journal}: Mol Genet Genomic Med
{Volume}: 12
{Issue}: 2
{Year}: 2024 Feb
{Factor}: 2.473
{DOI}: 10.1002/mgg3.2393
{Abstract}: <B>BACKGROUND: </B>Brachydactyly type E (BDE) is a general term characterized by variable shortening of metacarpals and metatarsals, with phalanges affected frequently. It can occur as an isolated form or part of syndromes and manifest a high degree of phenotypic variability. In this study, we have identified the clinical characteristics and pathogenic causes of a four-generation pedigree with 10 members affected by BDE and short stature.<BR><B>METHODS: </B>After the informed consent was signed, clinical data and peripheral blood samples were collected from available family members. Karyotype analysis, array-CGH, next-generation sequencing, and Sanger sequencing were employed to identity the pathogenic candidate gene.<BR><B>RESULTS: </B>No translocation or microdeletion/duplication was found in karyotype analysis and array-CGH; hence, a novel heterozygous mutation, c.146dupA. p.S50Vfs*22, was detected by next-generation sequencing in PTHLH gene, leading to a premature stop codon. Subsequently, the mutation was confirmed by Sanger sequencing and co-segregation analysis.<BR><B>CONCLUSIONS: </B>In this study, we described a novel heterozygous mutation (c.146dupA. p.S50Vfs*22) of gene PTHLH in a Chinese family. The mutation could induce a premature stop codon leading to a truncation of the protein. Our study broadened the mutation spectrum of PTHLH in BDE.