Adding evidence to the role of NEUROG1 in congenital cranial dysinnervation disorders. Issue 4 (20th January 2021)

• Record Type: Journal Article
• Authors: Dupont, Juliette; Vieira, José Pedro; Tavares, Ana Lisa Taylor; Conceição, Carla Ribeiro; Khan, Suliman; Bertoli‐Avella, Aida Maria; Sousa, Ana Berta
• Is Part Of: Clinical genetics. Volume 99:Issue 4(2021)
• Page Start: 588
• Page End: 593
• Publication Date: 2021-01-20
• Subjects: aplasia/hypoplasia of sensory cranial ganglia -- congenital cranial dysinnervation disorder -- NEUROG1 -- oromotor dysfunction -- sensorineural deafness -- trigeminal nerve aplasia/hypoplasia -- vestibulo‐cochlear nerve aplasia/hypoplasia; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13922
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: Congenital cranial dysinnervation disorders (CCDDs) are a heterogeneous group of neurodevelopmental phenotypes caused by a primary disturbance of innervation due to deficient, absent, or misguided cranial nerves. Although some CCDDs genes are known, several clinical phenotypes and their aetiologies remain to be elucidated. We describe a 12‐year‐old boy with hypotonia, developmental delay, sensorineural hearing loss, and keratoconjunctivitis due to lack of corneal reflex. He had a long expressionless face, severe oromotor dysfunction, bilateral agenesis/severe hypoplasia of the VIII nerve with marked atresia of the internal auditory canals and cochlear labyrinth malformation. Trio‐exome sequencing identified a homozygous loss of function variant in the NEUROG1 gene (NM_006161.2: c.202G > T, p.Glu68*). NEUROG1 is considered a causal candidate for CCDDs based on (i) the previous report of a patient with a homozygous gene deletion and developmental delay, deafness due to absent bilateral VIII nerves, and severe oromotor dysfunction; (ii) a second patient with a homozygous NEUROG1 missense variant and corneal opacity, absent corneal reflex and intellectual disability; and (iii) the knockout mouse model phenotype which highly resembles the disorder observed in humans. Our findings support the growing compelling evidence that loss of NEUROG1 leads to a very distinctive disorder of cranial nerves development. Abstract :