A homozygous truncating NALCN variant in two Afro-Caribbean siblings with hypotonia and dolichocephaly.
Am J Med Genet A
; 182(8): 1877-1880, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32618095
ABSTRACT
NALCN encodes a sodium ion leak channel expressed in the nervous system that conducts a persistent influx of sodium ions to facilitate action potential formation. Homozygous or compound heterozygous loss of function variants in NALCN cause infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1; OMIM 615419). Through exome and Sanger sequencing, we found two siblings of Afro-Caribbean ancestry who are homozygous for a known NALCN pathogenic variant, p.Arg735Ter, leading to failure to thrive, severe hypotonia, and dolichocephaly. The older sibling died suddenly without a known etiology after evaluation but before molecular diagnosis. An international collaboration originating from a resource limited Caribbean island facilitated molecular diagnosis. Due to its small population, geographical isolation, and low socioeconomic status, the island lacks many specialty medical services, including clinical genetics. Descriptions of genetic disorders affecting individuals of Afro-Caribbean ancestry are rarely reported in the medical literature. Diagnosis of IHPRF1 is important, as individuals with biallelic pathogenic NALCN variants are severely affected and potentially are at risk for cardiorespiratory arrest. Additionally, knowing the pathogenic variants allows the possibility of prenatal or preimplantation genetic diagnosis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transtornos Psicomotores
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Predisposição Genética para Doença
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Canais Iônicos
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Proteínas de Membrana
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Hipotonia Muscular
Tipo de estudo:
Diagnostic_studies
Limite:
Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article