Prenatal and postnatal phenotype of a pathologic variant in the ATP6AP1 gene

The ATP6AP1 gene encodes for ATPase H+ transporting protein. ATP6AP1 gene mutations are associated with congenital disorders of glycosylation (CDG) and can affect multiple organ system. Descriptions of postnatal phenotype include immunodeficiency, hepatopathy and cognitive impairment. No prenatal phenotype of these gene mutations has been described to date.

This is a description of the prenatal workup of an infant diagnosed with a X-linked ATP6AP1 gene mutation. First trimester ultrasound demonstrated a thickened nuchal translucency measured at 3.27 mm and dysmorphic spinal canal, corresponding to kyphoscoliosis finding postnatally. Findings from amniocentesis at 15 weeks included elevated amniotic fluid alpha-fetoprotein (AF-AFP) and positive acetylcholinesterase (AchE). Dilation of the aortic arch was seen on fetal echocardiogram at 20 weeks. Throughout the second trimester, a rim of fluid collection was seen under the skin covering the thoracic and lumbar fetal spine, consistent with a large Aplasia Cutis below the right scapula present at birth.

To our knowledge, this is the first description of prenatal phenotype of an X-linked ATP6AP1 gene mutation, and the association of this gene mutation with increased NT, elevated AF-AFP and AchE and Aplasia Cutis Congenita. This variant was submitted to ClinVar public database, submission ID: SUB6537411.