L1CAM whole gene deletion in a child with L1 syndrome. Issue 6 (25th March 2014)

• Record Type: Journal Article
• Authors: Chidsey, Brandalyn A.; Baldwin, Erin E.; Toydemir, Reha; Ahles, Lauren; Hanson, Heather; Stevenson, David A.
• Is Part Of: American journal of medical genetics. Volume 164:Issue 6(2014.)
• Page Start: 1555
• Page End: 1558
• Publication Date: 2014-03-25
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36474
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36474-sec-0001" sec-type="section"> <p>L1 syndrome is a group of overlapping, X‐linked disorders caused by mutations in <italic>L1CAM</italic>. Clinical phenotypes within L1 syndrome include X‐linked hydrocephalus with stenosis of the aqueduct of sylvius (HSAS); mental retardation, adducted thumbs, shuffling gait, and aphasia (MASA) syndrome; spastic paraplegia type 1; and agenesis of the corpus callosum. Over 200 mutations in <italic>L1CAM</italic> have been reported; however, only a few large gene deletions have been observed. We report on a 4‐month‐old male with a de novo whole gene deletion of <italic>L1CAM</italic> presenting with congenital hydrocephalus, aqueductal stenosis, and adducted thumbs. Initial failure of <italic>L1CAM</italic> gene sequencing suggested the possibility of a whole gene deletion of <italic>L1CAM</italic>. Further investigation through chromosome microarray analysis showed a 62Kb deletion encompassing the first exon of the <italic>PDZD4</italic> gene and the entire <italic>L1CAM</italic> gene. Investigations into genotype–phenotype correlations have suggested that mutations leading to truncated or absent L1 protein cause more severe forms of L1 syndrome. Based on the presentation of the proband and other reported patients with whole gene deletions, we provide further evidence that <italic>L1CAM</italic> whole gene deletions result in L1 syndrome with a severe phenotype, deletions of <italic>PDZD4</italic> do not cause additional manifestations, and that X‐linked nephrogenic diabetes insipidus reported in a subset of patients with large <italic>L1CAM</italic> deletions results from the loss of <italic>AVPR2</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>