ICNC Abstracts, ICNC 2018

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Delineation of the CLP1 mutations; A possible founder mutation in Turkish cohort
Sema Saltik, Serhat Guler, Tanyel Zubarioglu, Ertugrul Kiykim, Cengiz Yalcinkaya, Gözde Yesil

Last modified: 2018-09-09

Abstract


Purpose: We provide the clinical and molecular aspects of 5 new patients with CLP1 mutations suggesting a founder affect for the Turkish population.

Rationale: CLP1 gene is a RNA kinase involved in tRNA splicing. The affected individuals develop severe motor sensory defects, cortical dysgenesis and microcephaly.

CLP1 is a RNA kinase involved in tRNA splicing. CLP1 kinase-dead mice were shown to display a neuromuscular disorder with loss of motor neurons and muscle paralysis to a loss of CLP1 interaction with the tRNA splicing endonuclease (TSEN) complex, largely reduced pre tRNA cleavage activity, and accumulation of linear tRNA introns. The affected individuals develop severe motor-sensory deficits, cortical dysgenesis, and microcephaly.

Patients/Methods:  We report a series of 5 cases with CLP1 mutations out of 4 unrelated families.

Results: All patients were found to have the same mutation in CLP1 gene (c.G419A:p.R140H) suggesting a founder effect in Turkish populations. All had severe intellectual deficiency and developmental delay, truncal hypotonia and spasticity on four extremities. The birth head circumference were in normal ranges however developed microcephaly postnatally.  In 3 patients we have detected startle response, myoclonias we may be a novel symptom for this syndrome. 2 patient had low CSF aminoacid level specifically serine which was measured as 0 in one patient. All had disorganized EEG patterns.

Conclusion: Myoclonias with the absence of epileptic discharges is notable. It is important to detect these patients at earlies stages. Myoclonias and startle responses together with microcephaly and spasticity may be the clue for the diagnosis.


Keywords


CLP1 mutations; pontocerebellar hypoplasia; microcephaly

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