Abstract
BackgroundWe report on a 6-year-old Turkish boy with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild developmental delay. Further findings included scaphocephaly, plagiocephaly, long palpebral fissures, high narrow palate, low-set posteriorly rotated ears, torticollis, hypoplastic genitalia and faulty foot posture. Parents were consanguineous.Methods and resultsComputed tomography and magnetic resonance imaging showed bilateral single widened cochlear turn, narrowing of the internal auditory canal, and bilateral truncation of the vestibulo-cochlear nerve. Microarray analysis and next generation sequencing showed a homozygous deletion of chromosome 5q31.1 spanning 115.3 kb and including three genes: NEUROG1 (encoding neurogenin 1), DCNP1 (dendritic cell nuclear protein 1, C5ORF20) and TIFAB (TIFA-related protein). The inability to chew and swallow, deafness and balance disorder represented congenital palsies of cranial nerves V (trigeminal nerve) and VIII (vestibulo-cochlear nerve) and thus a congenital cranial dysinnervation disorder.ConclusionsBased on reported phenotypes of neurog1 null mutant mice and other vertebrates, we strongly propose NEUROG1 as the causative gene in this boy. The human NEUROG1 resides within the DFNB60 locus for non-syndromic autosomal recessive deafness on chromosome 5q22-q31, but linkage data have excluded it from being causative in the DFNB60 patients. Given its large size (35 Mb, >100 genes), the 5q22-q31 area could harbor more than one deafness gene. We propose NEUROG1 as a new gene for syndromic autosomal recessive hearing loss and congenital cranial dysinnervation disorder including cranial nerves V and VIII.
Highlights
We report on a 6-year-old Turkish boy with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild developmental delay
The human Neurogenin1 gene (NEUROG1) resides within the DFNB60 locus for non-syndromic autosomal recessive deafness on chromosome 5q22-q31, but linkage data have excluded it from being causative in the DFNB60 patients
We propose NEUROG1 as a new gene for syndromic autosomal recessive hearing loss and congenital cranial dysinnervation disorder including cranial nerves V and VIII
Summary
We report on a 6-year-old Turkish boy with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild developmental delay. The cranial sensory ganglia can be separated into two groups according to the origin of their constituent neurons. The proximal ganglia originate from the trigeminal and otic placodes and the neural crest, whereas the distal ganglia are derived from the other epibranchial placodes (facial, glossopharyngeal and vagus placode) [3]. The proximal ganglia include the ganglia for cranial nerves V, VIII and XI (trigeminal, vestibulo-cochlear and accessory nerves). Cranial nerve V (trigeminal nerve) includes motoric nerve fibers in addition to sensory ones; these are derived from the nucleus motorius nervi trigemini in the rhombencephalon. Neuronal development of all cranial sensory ganglia requires different basic helix-loop-helix transcription factors [5], including neurogenin (neurog1) and neurogenin (neurog2) [6]. Neurog was essential for the formation of the proximal cranial sensory neurons and neurog was found to be more involved in control of the distal cranial sensory neurons [8,9,10]
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