Birth defects research · 2022
Genotype-phenotype spectrum and correlations in Xia-Gibbs syndrome: Report of five novel cases and literature review.
Клинический случайОбзорПоддержка исследования: вне правительства СШАСтатьяНазвание и аннотация: Перевод в очереди
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Romano Ferruccio, Falco Mariateresa, Cappuccio Gerarda, Brunetti-Pierri Nicola, Lonardo Fortunato, Torella Annalaura, Digilio Maria Cristina, Dentici Maria Lisa, Alfieri Paolo, Agolini Emanuele, Novelli Antonio, Garavelli Livia, Accogli Andrea, TUDP, Striano Pasquale, Scarano Gioacchino, Nigro Vincenzo, Scala Marcello, Capra Valeria
Аннотация
BACKGROUND: Xia-Gibbs syndrome (XGS) is a rare neurodevelopmental disorder caused by pathogenic variants in the AT-hook DNA-binding motif-containing 1 gene (AHDC1), encoding a protein with a crucial role in transcription and epigenetic regulation, axonogenesis, brain function, and neurodevelopment. AHDC1 variants possibly act through a dominant-negative mechanism and may interfere with DNA repair processes, leading to genome instability and impaired DNA translesion repair. Variants affecting residues closer to the N-terminal are thought to determine a milder phenotype with better cognitive performances. However, clean-cut genotype-phenotype correlations are still lacking.
CASES: In this study, we investigated five subjects with XGS in whom exome sequencing led to the identification of five novel de novo pathogenic variants in AHDC1. All variants were extremely rare and predicted to cause a loss of protein function. The phenotype of the reported patients included developmental delay, hypotonia, and distinctive facial dysmorphisms. Additionally, uncommon clinical features were observed, including congenital hypothyroidism and peculiar skeletal abnormalities.
CONCLUSIONS: In this study, we report uncommon XGS features associated with five novel truncating variants in AHDC, thus expanding the genotype and phenotypic spectrum of this complex condition. We also compared our cases to previously reported cases, discussing the current status of genotype-phenotype correlations in XGS.
CASES: In this study, we investigated five subjects with XGS in whom exome sequencing led to the identification of five novel de novo pathogenic variants in AHDC1. All variants were extremely rare and predicted to cause a loss of protein function. The phenotype of the reported patients included developmental delay, hypotonia, and distinctive facial dysmorphisms. Additionally, uncommon clinical features were observed, including congenital hypothyroidism and peculiar skeletal abnormalities.
CONCLUSIONS: In this study, we report uncommon XGS features associated with five novel truncating variants in AHDC, thus expanding the genotype and phenotypic spectrum of this complex condition. We also compared our cases to previously reported cases, discussing the current status of genotype-phenotype correlations in XGS.