Scholarlink

<p>Osteogenesis Imperfecta (OI) is a genetically heterogeneous disorder with a clinical spectrum ranging from mild to severe. Biallelic <i>P3H1</i> (OMIM*610339) variants are generally associated with a severe recessive phenotype. This study reports six individuals from three families with phenotypic variability and two novel variants, aiming to expand the phenotypic and genotypic spectrum of <i>P3H1</i>-related OI. The six patients from three unrelated families exhibited varying severity of <i>P3H1</i>-related OI. In Family 1, three siblings, all homozygous for the recurrent c.446&#xa0;T &gt; G (p.Leu149Arg) variant, showed marked phenotypic differences. One presented with a deforming phenotype, while the other two had milder forms with fewer fractures and little to no skeletal deformity. In Family 2, the affected individual had neonatal fractures and was compound heterozygous for a novel splice-site variant (c.1171-2_1171-1delinsC) and a missense change previously classified as variant of uncertain significance (VUS) (c.1224G &gt; C; p.Lys408Asn). The variants were segregated confirming compound heterozygosity. In Family 3, two siblings with neonatal fractures were homozygous for a novel 58&#xa0;bp deletion in exon 15 (c.2112_2169del; p.Glu708AlafsTer21), with both parents identified as carriers. This study expands the <i>P3H1</i> genotypic spectrum with two novel variants and provides evidence supporting reclassification of c.1224G &gt; C as likely pathogenic based on the updated PM3 criterion. It highlights phenotypic variability in patients with the same variant and suggests mild phenotypes may be seen in patients with certain <i>P3H1</i> variants.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Expanding the Genotypic and Phenotypic Spectrum of P3H1 Related Osteogenesis Imperfecta

  • 期刊论文

  • 发表日期：

    2025年8月5日

查看全文
  • Erdem Kındış,
  • Enise Avcı Durmuşaliğlu,
  • Elif Eviz

摘要

Osteogenesis Imperfecta (OI) is a genetically heterogeneous disorder with a clinical spectrum ranging from mild to severe. Biallelic P3H1 (OMIM*610339) variants are generally associated with a severe recessive phenotype. This study reports six individuals from three families with phenotypic variability and two novel variants, aiming to expand the phenotypic and genotypic spectrum of P3H1-related OI. The six patients from three unrelated families exhibited varying severity of P3H1-related OI. In Family 1, three siblings, all homozygous for the recurrent c.446 T > G (p.Leu149Arg) variant, showed marked phenotypic differences. One presented with a deforming phenotype, while the other two had milder forms with fewer fractures and little to no skeletal deformity. In Family 2, the affected individual had neonatal fractures and was compound heterozygous for a novel splice-site variant (c.1171-2_1171-1delinsC) and a missense change previously classified as variant of uncertain significance (VUS) (c.1224G > C; p.Lys408Asn). The variants were segregated confirming compound heterozygosity. In Family 3, two siblings with neonatal fractures were homozygous for a novel 58 bp deletion in exon 15 (c.2112_2169del; p.Glu708AlafsTer21), with both parents identified as carriers. This study expands the P3H1 genotypic spectrum with two novel variants and provides evidence supporting reclassification of c.1224G > C as likely pathogenic based on the updated PM3 criterion. It highlights phenotypic variability in patients with the same variant and suggests mild phenotypes may be seen in patients with certain P3H1 variants.