{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T11:56:41Z","timestamp":1774958201508,"version":"3.50.1"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> The article aims to provide genetic counseling to a family with two children who were experiencing growth and developmental delays.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Clinical information of the proband was collected. Peripheral blood was collected from core family members to identify the initial reason for growth and developmental delays by whole exome sequencing (WES) and Sanger sequencing. To ascertain the consequences of the newly discovered variants, details of the variants detected were analyzed by bioinformatic tools. Furthermore, we performed <jats:italic>in vitro<\/jats:italic> experimentation targeting <jats:italic>SNX14<\/jats:italic> gene expression to confirm whether the variants could alter the expression of <jats:italic>SNX14<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The proband had prenatal ultrasound findings that included flattened frontal bones, increased interocular distance, widened bilateral cerebral sulci, and shortened long bones, which resulted in subsequent postnatal developmental delays. The older sister also displayed growth developmental delays and poor muscle tone. WES identified compound heterozygous variants of c.712A&amp;gt;T (p.Arg238Ter) and .2744A&amp;gt;T (p.Gln915Leu) in the <jats:italic>SNX14<\/jats:italic> gene in these two children. Both are novel missense variant that originates from the father and mother, respectively. Sanger sequencing confirmed this result. Following the guideline of the American College of Medical Genetics and Genomics (ACMG), the <jats:italic>SNX14<\/jats:italic> c.712A&amp;gt;T (p.Arg238Ter) variant was predicted to be pathogenic (P), while the <jats:italic>SNX14<\/jats:italic> c.2744A&amp;gt;T (p.Gln915Leu) variant was predicted to be a variant of uncertain significance (VUS). The structural analysis revealed that the c.2744A&amp;gt;T (p.Gln915Leu) variant may impact the stability of the <jats:italic>SNX14<\/jats:italic> protein. <jats:italic>In vitro<\/jats:italic> experiments demonstrated that both variants reduced <jats:italic>SNX14<\/jats:italic> expression.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The <jats:italic>SNX14<\/jats:italic> gene c.712A&amp;gt;T (p.Arg238Ter) and c.2744A&amp;gt;T (p.Gln915Leu) were identified as the genetic causes of growth and developmental delay in two affected children. This conclusion was based on the clinical presentations of the children, structural analysis of the mutant protein, and <jats:italic>in vitro<\/jats:italic> experimental validation. This discovery expands the range of <jats:italic>SNX14<\/jats:italic> gene variants and provides a foundation for genetic counseling and guidance for future pregnancies in the affected children\u2019s families.<\/jats:p>","DOI":"10.3389\/fgene.2024.1379366","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T04:34:16Z","timestamp":1712637256000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Compound heterozygous mutation of the SNX14 gene causes autosomal recessive spinocerebellar ataxia 20"],"prefix":"10.3389","volume":"15","author":[{"given":"Yuqi","family":"Shao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saisai","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiafu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanzhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/ng.3256","article-title":"Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction","volume":"47","author":"Akizu","year":"2015","journal-title":"Nat. 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