New syndromic combined immunodeficiency with severe neurodevelopmental defects caused by biallelic null variants in the PPM1D gene

PPM1D (protein phosphatase Mn2+/Mg2+-dependent 1D) is a phosphatase that targets proteins related to the DNA damage repair system. C-terminal variants in PPM1D have been associated with: i) malignancy as somatic variants; and ii) Jansen-de-Vries (JdV) syndrome as germline heterozygous variants. JdV syndrome curses with moderate neurodevelopmental alterations and behavioral problems, such as autistic spectrum disorders (ASD), without reports of immunodeficiency.