Lekárska genetika a diagnostika 2/2025
A novel deletion in the ATAD3 gene cluster as a cause of pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome in a newborn
Neonatal lethal pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency (PHRINL) is an autosomal recessive multisystem disorder with prenatal onset and death occurring in the neonatal period. In a male newborn who died shortly after birth, we detected a homozygous deletion affecting the ATAD3B and ATAD3A genes. Clinical exome analysis was performed using massively parallel sequencing of DNA from the proband’s peripheral blood, the mother, the father, and amniotic fluid from the mother’s ongoing pregnancy. Deletions were identified within the ATAD3 gene cluster. The father was a heterozygous carrier of a deletion spanning exons 4–16 of ATAD3B and exons 1–4 of ATAD3A, while the mother was a heterozygous carrier of a deletion involving exons 10–12 of ATAD3C, the entire ATAD3B gene (exons 1–16), and exons 1–2 of ATAD3A. The fetus from the current pregnancy inherited only the maternal variant. We identified novel, previously unreported deletions in the ATAD3 gene cluster in this family, present in both parents, whose overlap was the cause of the homozygous deletion in the first deceased child.
Keywords: ATAD3 gene cluster, pontocerebellar hypoplasia, neonatal respiratory insufficiency, clinical exome sequencing, NGS
