LETTER TO JMG

Deletion 9q34.3 syndrome: genotype-phenotype correlations and an extended deletion in a patient with features of Opitz C trigonocephaly

S A Yatsenko¹, S W Cheung¹, D A Scott^1,3, M J M Nowaczyk⁴, M Tarnopolsky^5,6, S Naidu^7,8, G Bibat⁸, A Patel¹, J G Leroy^1,9, F Scaglia^1,3, P Stankiewicz¹, J R Lupski^1,2,3

¹ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
² Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
³ Texas Children’s Hospital, Houston, TX, USA
⁴ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
⁵ Department of Medicine, McMaster University, Hamilton, Ontario, Canada
⁶ Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
⁷ Johns Hopkins University, Baltimore, MD, USA
⁸ Kennedy Krieger Institute, Baltimore, MD, USA
⁹ Department of Medical Genetics, Ghent University Hospital, Ghent, Belgium

Correspondence to:
Correspondence to:
Dr James R Lupski
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Room 604B, Houston, TX 77030, USA; jlupski@bcm.tmc.edu

Received 13 October 2004
Revised version received 24 November 2004

Accepted 25 November 2004

Abbreviations: ASD, atrial septal defect; BAC, bacterial artificial chromosome; CHD, congenital heart defects; FISH, fluorescence in situ hybridisation; GU, genito-urinary; IHH, idiopathic hypogonadotropic hypogonadism; LCR, low copy repeat; NVDCCs, N-type voltage dependent Ca²⁺ channels; OTCS, Opitz trigonocephaly C syndrome; SNP, single nucleotide polymorphism; SRO, shortest region of overlap; VSD, ventricular septal defect

Keywords: contiguous gene syndrome; deletion 9q34.3; genotype-phenotype correlation; Opitz trigonocephaly C syndrome; telomere

The first 150 words of the full text of this article appear below.

Submicroscopic deletion del(9)(q34.3) is a rare constitutional microdeletion syndrome involving the gene-rich subtelomeric region of the long arm of chromosome 9, with about 30 cases reported.^{1,2,3,4,5,6,7,8,9,10,11,12} Visible constitutional 9q34 deletions are extremely rare, with only a few cases described.^2,10,12 The low prevalence of large terminal deletions at the 9q34 chromosome region in liveborns is thought to reflect lethality in early embryogenesis.¹³

At least 18 patients with 9q34.3 microdeletions detected by fluorescence in situ hybridisation (FISH) testing, in whom normal karyotypes were initially obtained, have been reported.^1,5–7,11 Many patients carry a cryptic del(9)(q34.3) that may result in a clinically recognisable phenotype characterised by severe developmental delay, mental retardation, hypotonia, congenital heart defects (CHD), seizures, and prominent craniofacial features including microcephaly, arched eyebrows, hypertelorism, short nose with anteverted nostrils, open mouth, and a protruding tongue.^6,7,11 Recently, based on clinical and molecular breakpoint analyses using FISH, microsatellites, and single nucleotide polymorphism (SNP) genotyping, . . . [Full text of this article]

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