A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm

Moran Gal; Daniella Magen; Younan Zahran; Ayelet Eran; Morad Khayat; Chen Gafni; Erez Y. Levanon; Hanna Mandel; Sarit Ravidi

doi:10.1016/j.ejmg.2016.02.007

A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm

Moran Gal
, Daniella Magen
, Younan Zahran
, Ayelet Eran
, Morad Khayat
, Chen Gafni
, Erez Y. Levanon
, Hanna Mandel
, Sarit Ravidi

The Mina and Everard Goodman Faculty of Life Sciences - at Bar-Ilan University

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

We studied three siblings, born to consanguineous parents who presented with severe intellectual disability, cachexia, strabismus, seizures and episodes of abnormal respiratory rhythm. Whole exome sequencing led to identification of a novel homozygous splice site mutation, IVS29-1G > A in the NALCN gene, that resulted in aberrant transcript in the patients. NALCN encodes a voltage-independent cation channel, involved in regulation of neuronal excitability. Three homozygous mutations in the NALCN gene were previously identified in only eight patients with severe hypotonia, speech impairment, cognitive delay, constipation and Infantile-Neuroaxonal-dystrophy- like symptoms. Our patients broaden the clinical spectrum associated with recessive mutations in NALCN, featuring also disrupted respiratory rhythm mimicking homozygous Nalcn knockout mice.

Original language	English
Pages (from-to)	204-209
Number of pages	6
Journal	European Journal of Medical Genetics
Volume	59
Issue number	4
DOIs	https://doi.org/10.1016/j.ejmg.2016.02.007
State	Published - 1 Apr 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Masson SAS.

Funding

We Thanks Alona Zilberberg and Nurit Gal-Mark for their assistance with the cell lines culture and RNA extraction procedures. We thank Orly Elpeleg for reviewing the exome data and helpful suggestions. This work was supported by the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation [ 41/11 and 1796/12 ].

Funders	Funder number
Israel Science Foundation	41/11, 1796/12
Planning and Budgeting Committee of the Council for Higher Education of Israel

Keywords

Abnormal respiratory rhythm
Cachexia
Intellectual disability
NALCN gene
Seizures

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10.1016/j.ejmg.2016.02.007

Cite this

Gal, M., Magen, D., Zahran, Y., Eran, A., Khayat, M., Gafni, C., Levanon, E. Y., Mandel, H., & Ravidi, S. (2016). A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm. European Journal of Medical Genetics, 59(4), 204-209. https://doi.org/10.1016/j.ejmg.2016.02.007

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title = "A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm",

abstract = "We studied three siblings, born to consanguineous parents who presented with severe intellectual disability, cachexia, strabismus, seizures and episodes of abnormal respiratory rhythm. Whole exome sequencing led to identification of a novel homozygous splice site mutation, IVS29-1G > A in the NALCN gene, that resulted in aberrant transcript in the patients. NALCN encodes a voltage-independent cation channel, involved in regulation of neuronal excitability. Three homozygous mutations in the NALCN gene were previously identified in only eight patients with severe hypotonia, speech impairment, cognitive delay, constipation and Infantile-Neuroaxonal-dystrophy- like symptoms. Our patients broaden the clinical spectrum associated with recessive mutations in NALCN, featuring also disrupted respiratory rhythm mimicking homozygous Nalcn knockout mice.",

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Gal, M, Magen, D, Zahran, Y, Eran, A, Khayat, M, Gafni, C, Levanon, EY, Mandel, H & Ravidi, S 2016, 'A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm', European Journal of Medical Genetics, vol. 59, no. 4, pp. 204-209. https://doi.org/10.1016/j.ejmg.2016.02.007

A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm. / Gal, Moran; Magen, Daniella; Zahran, Younan et al.
In: European Journal of Medical Genetics, Vol. 59, No. 4, 01.04.2016, p. 204-209.

Research output: Contribution to journal › Article › peer-review

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AU - Eran, Ayelet

AU - Khayat, Morad

AU - Gafni, Chen

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AU - Mandel, Hanna

AU - Ravidi, Sarit

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A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm

Abstract

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Keywords

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