ABSTRACT
HK1 deficient Haemolytic Anaemia in association with a Neurological Phenotype & co-existing Meckel-Gruber due to CEP290 in a Romani family.
Subject(s)
Anemia, Hemolytic/diagnosis , Anemia, Hemolytic/genetics , Antigens, Neoplasm/genetics , Cell Cycle Proteins/genetics , Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/genetics , Cytoskeletal Proteins/genetics , Encephalocele/diagnosis , Encephalocele/genetics , Hexokinase/genetics , Mutation , Phenotype , Polycystic Kidney Diseases/diagnosis , Polycystic Kidney Diseases/genetics , Retinitis Pigmentosa/diagnosis , Retinitis Pigmentosa/genetics , Alleles , Amino Acid Substitution , Genetic Association Studies , Genetic Predisposition to Disease , Humans , PedigreeABSTRACT
We describe an X-linked syndrome in 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with intrauterine growth retardation, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. We performed genome sequencing in four individuals and identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals. OTUD5 was considered as a candidate gene based on two previous missense variants detected in patients with intellectual disability. In conclusion, we define a syndrome associated with OTUD5 defects and add compelling evidence of genotype-phenotype association. This finding ended the long diagnostic odyssey of this family.
