TASP1 is deleted in an infant with developmental delay, microcephaly, distinctive facial features, and multiple congenital anomalies

Abstract

We report a 20p12.1 homozygous deletion including exons 5-10 of the TASP1 gene in an infant with developmental delay, acquired microcephaly, distinctive facial features, and multiple congenital anomalies involving skeletal, cardiac, and renal systems. TASP1 encodes taspase 1 which is responsible for cleaving, thus activating, a number of transcription factors including the mixed lineage leukemia 1 (MLL1). Taspase 1-deficient mice showed early lethality, skeletal abnormalities, and growth failure, which support a potentially causal role of TASP1 deletion in this infant. Furthermore, the infant reported here had many of the features seen in Wiedemann-Steiner syndrome which is caused by MLL1 defects. Such observation further supports that TASP1 is a novel disease-related gene that is associated with a disease phenotype overlapping with Wiedemann-Steiner syndrome as both are caused by defects in the same pathway.

Homozygous loss‐of‐function variants of TASP1 , a gene encoding an activator of the histone methyltransferases KMT2A and KMT2D, cause a syndrome of developmental delay, happy demeanor, distinctive facial features, and congenital anomalies

“…Furthermore, no coverage was obtained by WES for a part of TASP1 , which is consistent with the homozygous deletion affecting this gene. This child was previously reported at an earlier age (Suleiman, Mundt, Sampath, & El‐Hattab, ).…”

Taspase1 orchestrates fetal liver hematopoietic stem cell and vertebrae fates through cleaving TFIIA

“…Recently, a novel human hereditary anomaly syndrome was recognized in association with loss-of-function mutations in the TASP1 gene (1)(2)(3). Those patients were characterized with microcephaly, developmental delay, distinctive facial features, and other anomalies including anemia, thrombocytopenia and lymphocytopenia (2,3).…”

TASP1 mutation in a female with craniofacial anomalies, anterior segment dysgenesis, congenital immunodeficiency and macrocytic anemia

“…This child had excess forehead hair, arched and thick eyebrows, synophrys, a broad nasal bridge, downslanted palpebral fissures, wide‐set eyes, epicanthus, low‐set ears, an overfolded right ear helix, microretrognathia, thin upper lip and downturned corners of mouth. A left‐sided preauricular skin tag, webbed neck, preaxial polydactyly of the right hand and bilateral single palmar creases were also observed (Suleiman et al, ). Echocardiography demonstrated a small patent foramen ovale with a left to right shunt and a ventricular septal defect, while renal sonography revealed mild left‐sided hydronephrosis.…”

“…There is only one other reported case with deleterious variants in TASP1 . An infant with developmental delay, acquired microcephaly, distinctive facial features, and multiple congenital anomalies involving skeletal, cardiac, and renal systems was found to harbor a homozygous deletion including exons five to 10 of TASP1 (Suleiman, Mundt, Sampath, & El‐Hattab, ). This child had excess forehead hair, arched and thick eyebrows, synophrys, a broad nasal bridge, downslanted palpebral fissures, wide‐set eyes, epicanthus, low‐set ears, an overfolded right ear helix, microretrognathia, thin upper lip and downturned corners of mouth.…”