Titel: Novel OTUD5 variant detected in a patient with multiple congenital anomalies-neurodevelopmental syndrome and suggested in a fetus in the same family
ID: P-ClinG-066
Art: Postertalk
Redezeit: 2 min
Session: Poster Session
ClinG 2

Referent: Irina Hüning (Lübeck/DE)

Abstract - Text


The OTUD5 gene at Xp11.23 encodes ovarian tumor deubiquitinase 5 protein, which is a deubiquitinating enzyme member of the ovarian tumor family. Recently 3 families with 16 male patients were reported, affected by a new X-linked recessive disorder (Multiple congenital anomalies-neurodevelopmental syndrome; MCAND; OMIM 301056), arising from pathogenic missense OTUD5 variants (Tripolszki et al. Clin Genet. 2021; Saida et al. Front Cell Dev Biol. 2021). Here, we report on a 29-year-old male patient with MCAND and a truncating variant in OTUD5 as well as a male fetus of the same family, a putative carrier of the same variant.

The index patient presents with severe intellectual impairment, hypotonia, distinctive dysmorphic facial features (hypertelorism, epicanthus, ptosis, blepharophimosis, wide nasal ridge, bulbous nose, high insertion of columella), intrauterine growth retardation, scoliosis, strabismus, bifid tongue, tetralogy of Fallot, single transverse palmar crease, self-injurious behavior, hypoplasia of corpus callosum, cryptorchidism and short stature. Single exome analysis of lymphocyte DNA showed the hemizygous variant OTUD5: c.1492C>T; p.(Gln498*).  

In 1990 the mother of the patient had a spontaneous abortion at 14 weeks of gestation. The pathological examination of the male fetus showed facial dysmorphic features with hypertelorism as well as growth retardation, postaxial polydactyly of the left foot, cleft palate, paramedian labial pits and broad thumbs. The cytogenetic analysis revealed a male karyotype 46,XY. Unfortunately fetal DNA was no more available for molecular analysis.

The phenotype of the index patient is very similar to the phenotype of patients with missense variants in OTUD5 recently described in the literature. Also the phenotype of the fetus is consistent with the features from the literature. Molecular analysis of OTUD5 in the unaffected mother is pending.

Here, we report on two additional patients with MCAND and a novel truncating variant in OTUD5 in the index patient, suggesting that also truncating variants in OTUD5 are responsible for MCAND and supporting the data on intrafamilial variability.