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<p>Ghosal hematodiaphyseal dysplasia (GHDD) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in TBXAS1, characterized by bone marrow failure and skeletal dysplasia. Phenotypic heterogeneity and limited case numbers have constrained understanding of genotype–phenotype correlations. We retrospectively analyzed five patients (four children and one adult) diagnosed with GHDD. Clinical features, laboratory parameters, radiologic findings, bone marrow morphology, genetic variants, treatment, and outcomes were reviewed. Molecular diagnosis was established using next-generation sequencing with American College of Medical Genetics and Genomics- based variant classification. Median age at presentation was 6 years; 60% were female and 60% had consanguinity. All patients presented with anemia, while thrombocytopenia and organomegaly were seen in 80%, and skeletal changes in 60%. Bone marrow findings were heterogeneous, including hypocellularity (40%), fibrosis (40%), and osteosclerosis (20%). Four TBXAS1 variants were identified, most commonly p.Arg412Gln; compound heterozygosity correlated with severe marrow pathology, while skeletal changes clustered with homozygous p.Arg412Gln or compound variants, and all patients rapidly responded to corticosteroids. This series expands the clinical and molecular spectrum of TBXAS1-associated GHDD, highlighting marked phenotypic variability and consistent steroid responsiveness. Early genetic evaluation in unexplained cytopenias is crucial for timely diagnosis and management.</p>

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TBXAS1-Associated Ghosal Hematodiaphyseal Dysplasia: A Case Series Exploring Genotype–Phenotype Correlation in Five Patients

  • 期刊论文

  • 发表日期：

    2026年5月18日

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  • Ekta Jajodia,
  • Ankit Jitani,
  • Tuphan Kanti Dolai,
  • Neeraj Arora,
  • Raj Shingala,
  • Kaustav Ghosh

摘要

Ghosal hematodiaphyseal dysplasia (GHDD) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in TBXAS1, characterized by bone marrow failure and skeletal dysplasia. Phenotypic heterogeneity and limited case numbers have constrained understanding of genotype–phenotype correlations. We retrospectively analyzed five patients (four children and one adult) diagnosed with GHDD. Clinical features, laboratory parameters, radiologic findings, bone marrow morphology, genetic variants, treatment, and outcomes were reviewed. Molecular diagnosis was established using next-generation sequencing with American College of Medical Genetics and Genomics- based variant classification. Median age at presentation was 6 years; 60% were female and 60% had consanguinity. All patients presented with anemia, while thrombocytopenia and organomegaly were seen in 80%, and skeletal changes in 60%. Bone marrow findings were heterogeneous, including hypocellularity (40%), fibrosis (40%), and osteosclerosis (20%). Four TBXAS1 variants were identified, most commonly p.Arg412Gln; compound heterozygosity correlated with severe marrow pathology, while skeletal changes clustered with homozygous p.Arg412Gln or compound variants, and all patients rapidly responded to corticosteroids. This series expands the clinical and molecular spectrum of TBXAS1-associated GHDD, highlighting marked phenotypic variability and consistent steroid responsiveness. Early genetic evaluation in unexplained cytopenias is crucial for timely diagnosis and management.