Decreased nasal nitric oxide in children with isolated midline neuroanatomical defects: a possible indicator of ciliary dysfunction?
CPS ePoster Library. Scott O. 06/25/15; 99110; 47
Ori Scott
Ori Scott
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Abstract
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Background: Cilia are microtubule-based structures marking the surfaces of most eukaryotic cell types, with crucial roles in cell-division, axis-determination, migration and differentiation. Ciliary mutations give rise to a spectrum of human disorders, collectively termed ‘ciliopathies’, with which midline neuroanatomical defects are strongly associated. However, an association between isolated neuroanatomical defects and ciliary dysfunction has never been proven. One test for ciliary function is measurement of nasal nitric oxide, which correlates with mean ciliary beat frequency.
It is a sensitive, non-invasive test, currently used in screening for Primary Ciliary Dyskinesia.
Objectives: to determine whether children with congenital isolated midline neuroanatomical defects suffer from ciliary dysfunction, using measurement of nasal nitric oxide.
Methods: We measured the nasal nitric oxide levels of 26 children ages 6-17, with congenital midline central nervous system defects, who are otherwise healthy. We evaluated the effect of a number of variables including: age, gender, and anomaly (brain, spinal cord, or combined) on our measurements. We compared our results to the previously established normal range (153.6-509.9 nL/min), and to the cutoff for children with Primary Ciliary Dyskinesia (77 nL/min).
Results: The overall range for nasal nitric oxide in our cohort was 56.5 to 334.7 nL/min, with age, gender, and anomaly not having a significant effect on the result. The overall mean, 217.7 nL/min, was significantly lower than the pre-established mean in normal children of the same age, 314.51 nL/min (p<0.05). Four subjects (15.4%) had mean nitric oxide levels below the lower end of normal, with two (7.7%) having values below the cutoff for Primary Ciliary Dyskinesia.
Conclusions: This is the first study reporting an association between ciliary dysfunction and isolated congenital midline neuroanatomical defects, not in the context of any known syndrome or ciliopathy. A possible candidate underlying both includes tubulin, a gene family encoding the microtubule alpha and beta subunits, necessary for proper ciliary formation. The tubulin gene products play a pivotal role in neuronal migration, cortical laminar organization, and guidance of radial glia, and their mutations were shown to result in a number of neuroanatomical malformations. Further studies are warranted to investigate this possible genetic link. From a clinical perspective, longitudinal studies will be required to determine whether nasal ciliary dysfunction in children with congenital midline brain anomalies has any clinical bearing on their respiratory function later in life.
Background: Cilia are microtubule-based structures marking the surfaces of most eukaryotic cell types, with crucial roles in cell-division, axis-determination, migration and differentiation. Ciliary mutations give rise to a spectrum of human disorders, collectively termed ‘ciliopathies’, with which midline neuroanatomical defects are strongly associated. However, an association between isolated neuroanatomical defects and ciliary dysfunction has never been proven. One test for ciliary function is measurement of nasal nitric oxide, which correlates with mean ciliary beat frequency.
It is a sensitive, non-invasive test, currently used in screening for Primary Ciliary Dyskinesia.
Objectives: to determine whether children with congenital isolated midline neuroanatomical defects suffer from ciliary dysfunction, using measurement of nasal nitric oxide.
Methods: We measured the nasal nitric oxide levels of 26 children ages 6-17, with congenital midline central nervous system defects, who are otherwise healthy. We evaluated the effect of a number of variables including: age, gender, and anomaly (brain, spinal cord, or combined) on our measurements. We compared our results to the previously established normal range (153.6-509.9 nL/min), and to the cutoff for children with Primary Ciliary Dyskinesia (77 nL/min).
Results: The overall range for nasal nitric oxide in our cohort was 56.5 to 334.7 nL/min, with age, gender, and anomaly not having a significant effect on the result. The overall mean, 217.7 nL/min, was significantly lower than the pre-established mean in normal children of the same age, 314.51 nL/min (p<0.05). Four subjects (15.4%) had mean nitric oxide levels below the lower end of normal, with two (7.7%) having values below the cutoff for Primary Ciliary Dyskinesia.
Conclusions: This is the first study reporting an association between ciliary dysfunction and isolated congenital midline neuroanatomical defects, not in the context of any known syndrome or ciliopathy. A possible candidate underlying both includes tubulin, a gene family encoding the microtubule alpha and beta subunits, necessary for proper ciliary formation. The tubulin gene products play a pivotal role in neuronal migration, cortical laminar organization, and guidance of radial glia, and their mutations were shown to result in a number of neuroanatomical malformations. Further studies are warranted to investigate this possible genetic link. From a clinical perspective, longitudinal studies will be required to determine whether nasal ciliary dysfunction in children with congenital midline brain anomalies has any clinical bearing on their respiratory function later in life.
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