{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:23:00Z","timestamp":1790522580832,"version":"4.1.0"},"reference-count":8,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"St. George's University Small Research Grant Initiative","award":["18017"],"award-info":[{"award-number":["18017"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>NALCN<\/jats:italic> 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 <jats:italic>NALCN<\/jats:italic> cause infantile hypotonia with psychomotor retardation and characteristic facies\u20101 (IHPRF1; OMIM 615419). Through exome and Sanger sequencing, we found two siblings of Afro\u2010Caribbean ancestry who are homozygous for a known <jats:italic>NALCN<\/jats:italic> 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\u2010Caribbean ancestry are rarely reported in the medical literature. Diagnosis of IHPRF1 is important, as individuals with biallelic pathogenic <jats:italic>NALCN<\/jats:italic> 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.<\/jats:p>","DOI":"10.1002\/ajmg.a.61744","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T06:26:21Z","timestamp":1593757581000},"page":"1877-1880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A homozygous truncating <scp><i>NALCN<\/i><\/scp> variant in two <scp>Afro\u2010Caribbean<\/scp> siblings with hypotonia and dolichocephaly"],"prefix":"10.1002","volume":"182","author":[{"given":"Omotayo","family":"Ope","sequence":"first","affiliation":[{"name":"Department of Biochemistry St. George's University School of Medicine  St. George's Grenada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-3507","authenticated-orcid":false,"given":"Elizabeth 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