Subtelomeric deletions of chromosome 9q: A novel microdeletion syndrome

Fluorescent in situ hybridization (FISH) screening of subtelomeric rearrangements has resulted in the identification of previously unrecognized chromosomal causes of mental retardation with and without dysmorphic features. This article reports the phenotypic and molecular breakpoint characterization in a cohort of 12 patients with subtelomeric deletions of chromosome 9q34. The phenotypic findings are consistent amongst these individuals and consist of mental retardation, distinct facial features and congenital heart defects (primarily conotruncal defects). Detailed breakpoint mapping by FISH, microsatellite and single nucleotide polymorphism (SNP) genotyping analysis has narrowed the commonly deleted region to an approximately 1.2 Mb interval containing 14 known transcripts. The majority of the proximal deletion breakpoints fall within a 400 kb interval between SNP markers C12020842 proximally and C80658 distally suggesting a common breakpoint in this interval. © 2004 Wiley‐Liss, Inc.

[1]  D. Warburton,et al.  Catalogue of unbalanced chromosome aberrations in man , 2004 .

[2]  A. Aylsworth,et al.  Submicroscopic deletion 9(q34.4) and duplication 19(p13.3): Identified by subtelomere specific FISH probes , 2004, American journal of medical genetics. Part A.

[3]  E. Mayatepek,et al.  A novel 5q35.3 subtelomeric deletion syndrome , 2003, American journal of medical genetics. Part A.

[4]  B. D. de Vries,et al.  Telomeres: a diagnosis at the end of the chromosomes , 2003, Journal of medical genetics.

[5]  L. Shaffer,et al.  Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome. , 2003, American journal of human genetics.

[6]  A. Munnich,et al.  Cryptic terminal deletion of chromosome 9q34: a novel cause of syndromic obesity in childhood? , 2003, Journal of medical genetics.

[7]  A. Jauch,et al.  Study of 30 patients with unexplained developmental delay and dysmorphic features or congenital abnormalities using conventional cytogenetics and multiplex FISH telomere (M-TEL) integrity assay , 2002, Human Genetics.

[8]  R. Hennekam,et al.  Further delineation of the chromosome 14q terminal deletion syndrome. , 2002, American journal of medical genetics.

[9]  E. Blennow,et al.  Subtelomeric rearrangements detected in patients with idiopathic mental retardation. , 2002, American journal of medical genetics.

[10]  E. Haan,et al.  Study of 250 children with idiopathic mental retardation reveals nine cryptic and diverse subtelomeric chromosome anomalies. , 2002, American journal of medical genetics.

[11]  R. Weksberg,et al.  Detecting rearrangements in children using subtelomeric FISH and SKY. , 2002, American journal of medical genetics.

[12]  R. Tenconi,et al.  Genotype-phenotype correlation in patients with NF1 microdeletion syndrome: identification of candidate genes for mental retardation , 2002 .

[13]  V. Siu,et al.  Detection of submicroscopic aberrations in patients with unexplained mental retardation by fluorescence in situ hybridization using multiple subtelomeric probes , 2001, Genetics in Medicine.

[14]  A. Munnich,et al.  Comparative genomic hybridisation in mentally retarded patients with dysmorphic features and a normal karyotype , 2001, Clinical genetics.

[15]  A. Verloes,et al.  Submicroscopic terminal deletions and duplications in retarded patients with unclassified malformation syndromes , 2001, Human Genetics.

[16]  C. Romano,et al.  Cryptic telomeric rearrangements in subjects with mental retardation associated with dysmorphism and congenital malformations , 2001, Journal of medical genetics.

[17]  A. Munnich,et al.  A novel automated strategy for screening cryptic telomeric rearrangements in children with idiopathic mental retardation , 2001, European Journal of Human Genetics.

[18]  B. D. de Vries,et al.  Submicroscopic subtelomeric 1qter deletions: a recognisable phenotype? , 2001, Journal of medical genetics.

[19]  M. Fichera,et al.  How microsatellite analysis can be exploited for subtelomeric chromosomal rearrangement analysis in mental retardation , 2001, Journal of medical genetics.

[20]  B. Marino,et al.  Congenital heart disease and genetic syndromes: specific correlation between cardiac phenotype and genotype. , 2000, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[21]  J. Flint,et al.  Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis , 2000, Journal of medical genetics.

[22]  E. Eichler,et al.  Structure of chromosomal duplicons and their role in mediating human genomic disorders. , 2000, Genome research.

[23]  L. Biesecker,et al.  Detection of chromosomal aberrations by a whole-genome microsatellite screen. , 2000, American journal of human genetics.

[24]  U. Francke,et al.  A physical map, including a BAC/PAC clone contig, of the Williams-Beuren syndrome--deletion region at 7q11.23. , 2000, American journal of human genetics.

[25]  Jonathan Flint,et al.  Subtle chromosomal rearrangements in children with unexplained mental retardation , 1999, The Lancet.

[26]  J. Flint,et al.  Screening for submicroscopic chromosome rearrangements in children with idiopathic mental retardation using microsatellite markers for the chromosome telomeres , 1999, Journal of medical genetics.

[27]  J. Lupski.  Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. , 1998, Trends in genetics : TIG.

[28]  L. Shaffer,et al.  Chromosome 1p36 deletions: the clinical phenotype and molecular characterization of a common newly delineated syndrome. , 1997, American journal of human genetics.

[29]  B. Roe,et al.  Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains. , 1997, Human molecular genetics.

[30]  E. Maltby,et al.  A report of a child with a deletion (9)(q34.3): a recognisable phenotype? , 1997, Journal of medical genetics.

[31]  Colin C. Collins,et al.  Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1 , 1997, Nature Genetics.

[32]  I. Krantz,et al.  Deletions of 20p12 in Alagille syndrome: frequency and molecular characterization. , 1997, American journal of medical genetics.

[33]  J. Flint,et al.  The relationship between chromosome structure and function at a human telomeric region , 1997, Nature Genetics.

[34]  D. Ledbetter,et al.  A complete set of human telomeric probes and their clinical application , 1996, Nature Genetics.

[35]  J. Flint,et al.  The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation , 1995, Nature Genetics.

[36]  D. Macer,et al.  Sense, nonsense and antisense. , 1994, Trends in genetics : TIG.

[37]  B. Hirsch,et al.  Infant with multiple congenital anomalies and deletion (9)(q34.3). , 1994, American journal of medical genetics.

[38]  G. Bernardi,et al.  The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[39]  P. Lichter,et al.  Chromosome analysis by non-isotopic in situ hybridization. , 1992 .

[40]  W. Brown,et al.  Stable length polymorphism of up to 260 kb at the tip of the short arm of human chromosome 16 , 1991, Cell.