Mutations in NALCN Cause an Autosomal-Recessive Syndrome with Severe Hypotonia, Speech Impairment, and Cognitive Delay

Moeenaldeen D. Al-Sayed; Hamad Al-Zaidan; AlBandary Albakheet; Hana Hakami; Rosan Kenana; Yusra Al-Yafee; Mazhor Al-Dosary; Alya Qari; Tarfa Al-Sheddi; Muhammed Al-Muheiza; Wafa Al-Qubbaj; Yamina Lakmache; Hindi Al-Hindi; Muhammad Ghaziuddin; Dilek Colak; Namik Kaya

doi:10.1016/j.ajhg.2013.08.001

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Mutations in NALCN Cause an Autosomal-Recessive Syndrome with Severe Hypotonia, Speech Impairment, and Cognitive Delay

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Mutations in NALCN Cause an Autosomal-Recessive Syndrome with Severe Hypotonia, Speech Impairment, and Cognitive Delay

Moeenaldeen D. Al-Sayed, Hamad Al-Zaidan, AlBandary Albakheet, Hana Hakami, Rosan Kenana, Yusra Al-Yafee, Mazhor Al-Dosary, Alya Qari, Tarfa Al-Sheddi, Muhammed Al-Muheiza, …

American journal of human genetics, Vol.93(4), pp.721-726

03/10/2013

DOI: https://doi.org/10.1016/j.ajhg.2013.08.001

PMCID: PMC3791267

PMID: 24075186

Abstract

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Sodium leak channel, nonselective (NALCN) is a voltage-independent and cation-nonselective channel that is mainly responsible for the leaky sodium transport across neuronal membranes and controls neuronal excitability. Although NALCN variants have been conflictingly reported to be in linkage disequilibrium with schizophrenia and bipolar disorder, to our knowledge, no mutations have been reported to date for any inherited disorders. Using linkage, SNP-based homozygosity mapping, targeted sequencing, and confirmatory exome sequencing, we identified two mutations, one missense and one nonsense, in NALCN in two unrelated families. The mutations cause an autosomal-recessive syndrome characterized by subtle facial dysmorphism, variable degrees of hypotonia, speech impairment, chronic constipation, and intellectual disability. Furthermore, one of the families pursued preimplantation genetic diagnosis on the basis of the results from this study, and the mother recently delivered healthy twins, a boy and a girl, with no symptoms of hypotonia, which was present in all the affected children at birth. Hence, the two families we describe here represent instances of loss of function in human NALCN .

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Title: Mutations in NALCN Cause an Autosomal-Recessive Syndrome with Severe Hypotonia, Speech Impairment, and Cognitive Delay
Creators - without role: Moeenaldeen D. Al-Sayed - Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Biostatistics, Epidemiology, and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Mental Health, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
Hamad Al-Zaidan - King Faisal Specialist Hospital & Research Centre
AlBandary Albakheet - Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Biostatistics, Epidemiology, and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Mental Health, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
Hana Hakami - King Faisal Specialist Hospital & Research Centre
Rosan Kenana - King Faisal Specialist Hospital & Research Centre
Yusra Al-Yafee - Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Biostatistics, Epidemiology, and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia Department of Mental Health, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
Mazhor Al-Dosary - King Faisal Specialist Hospital & Research Centre
Alya Qari - King Faisal Specialist Hospital & Research Centre
Tarfa Al-Sheddi - King Faisal Specialist Hospital & Research Centre
Muhammed Al-Muheiza - King Faisal Specialist Hospital & Research Centre
Wafa Al-Qubbaj - King Faisal Specialist Hospital & Research Centre
Yamina Lakmache - King Faisal Specialist Hospital & Research Centre
Hindi Al-Hindi - King Faisal Specialist Hospital & Research Centre
Muhammad Ghaziuddin - King Faisal Specialist Hospital & Research Centre
Dilek Colak - King Faisal Specialist Hospital & Research Centre
Namik Kaya - King Faisal Specialist Hospital & Research Centre
Publication Details: American journal of human genetics, Vol.93(4), pp.721-726
Publisher: Elsevier
Identifiers: 9913447808331
Academic Unit: King Faisal University; Alfaisal University
Language: English
Resource Type: Journal article