Further delineation of genotype–phenotype correlation in homozygous 2p21 deletion syndromes: First description of patients without cystinuria. Issue 8 (21st June 2013)

• Record Type: Journal Article
• Authors: Bartholdi, Deborah; Asadollahi, Reza; Oneda, Beatrice; Schmitt‐Mechelke, Thomas; Tonella, Paolo; Baumer, Alessandra; Rauch, Anita
• Is Part Of: American journal of medical genetics. Volume 161:Issue 8(2013:Aug.)
• Page Start: 1853
• Page End: 1859
• Publication Date: 2013-06-21
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.35994
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="ajmga35994-sec-0001" sec-type="section"> <p>Homozygous contiguous gene deletion syndromes are rare. On 2p21, however, several overlapping homozygous gene deletion syndromes have been described, all presenting with cystinuria but otherwise distinct phenotypes. Hypotonia‐cystinuria syndrome (HCS, OMIM606407) is characterized by infantile hypotonia, poor feeding, and growth hormone deficiency. Affected individuals carry homozygous deletions including the cystinuria gene <italic>SLC3A1</italic> and the adjacent <italic>PREPL</italic> gene. Larger homozygous deletions in this region encompassing the <italic>PPM1B</italic>, <italic>SLC3A1</italic>, <italic>PREPL</italic>, and <italic>C2orf34</italic> (<italic>CAMKMT</italic>) genes result in a more severe phenotype, the 2p21 deletion syndrome. A phenotype intermediate to HCS and the 2p21 deletion syndrome is termed atypical HCS and is caused by deletion of <italic>SLC3A1</italic>, <italic>PREPL</italic>, and <italic>C2orf34</italic> (<italic>CAMKMT</italic>). Using high resolution SNP array molecular karyotyping we identified two siblings with a homozygous deletion of 83 kb partially encompassing the genes <italic>PREPL</italic> and <italic>C2orf34</italic> (<italic>CAMKMT</italic>), but not the <italic>SLC3A1</italic> gene. The affected siblings display a recognizable phenotype which is similar to atypical HCS with regard to growth failure and neuro‐muscular features, but is characterized by lack of cystinuria. The patients also exhibit features which have not been reported to date such as cleft palate and genital abnormalities. In conclusion, we report the first patients with a homozygous 2p21 deletion syndrome without cystinuria and further delineate the complex genotype–phenotype correlations of homozygous microdeletion syndromes of this region. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>