A novel mosaic NSD1 intragenic deletion in a patient with an atypical phenotype12. Issue 3 (22nd January 2013)

• Record Type: Journal Article
• Authors: Castronovo, Chiara; Rusconi, Daniela; Crippa, Milena; Giardino, Daniela; Gervasini, Cristina; Milani, Donatella; Cereda, Anna; Larizza, Lidia; Selicorni, Angelo; Finelli, Palma
• Is Part Of: American journal of medical genetics. Volume 161:Issue 3(2013:Mar.)
• Page Start: 611
• Page End: 618
• Publication Date: 2013-01-22
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.35814
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Sotos syndrome, which is characterized by overgrowth, macrocephaly, distinctive facial features, and developmental delay, arises from mutations and deletions of the <italic>NSD1</italic> gene at 5q35.3. Sixteen <italic>NSD1</italic> intragenic deletions (including one in a mosaic condition) and one partial duplication have been reported in patients with Sotos syndrome. Here, we describe a boy aged 4 years and 10 months that showed facial dysmorphism (including frontal bossing, widely spaced eyes, deeply set eyes, a wide nasal bridge, anteverted nares, and a wide mouth), normal growth, and a psychomotor delay. High‐resolution array comparative genomic hybridization (CGH) analysis identified a mosaic heterozygous intragenic <italic>NSD1</italic> deletion of 38 kb, which included part of intron 2 and the entire exon 3, and led to <italic>NSD1</italic> haploinsufficiency. The deletion somatic mosaicism was subsequently confirmed by fluorescence in situ hybridization (FISH) analysis using fosmid clones. This patient presents the most atypical phenotype thus far associated with <italic>NSD1</italic> haploinsufficiency. It is possible that this atypical phenotype may have resulted from the somatic mosaicism of the <italic>NSD1</italic> defect. Our study confirms the usefulness of array CGH for increasing the detection rate of <italic>NSD1</italic> abnormalities and for diagnosing syndromic patients that do not present an easily recognized phenotype. © 2013 Wiley Periodicals, Inc.</p> </abstract>