A child with features of Goldenhar syndrome and a novel 1.12 Mb deletion in 22q11.2 by cytogenetics and oligonucleotide array CGH: Is this a candidate region for the syndrome?

Xu, Jie; Fan, Yao Shan; Siu, Victoria Mok

doi:10.1002/ajmg.a.32359

Cited by 53 publications

(67 citation statements)

References 12 publications

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“…Based on the recently demonstrated role of structural variants in the etiology of complex diseases (Sebat et al 2007;Blauw et al 2008) and the presence of microdeletions in some sporadic cases with features of OAVS (Ala-Mello et al 2008;Xu et al 2008;Rooryck et al 2009;Huang et al 2010), we attempted to use high-density SNP-genotype data to determine the structural variation in this family, and found no significant differences of the CNV number and size between the affected and unaffected individuals. Although five CNVs (in 1q21.3, 9p11.2, 10q11.22, 11q11, and 13q31.1) were present in patients at higher ratios, they were also seen in unaffected family members.…”

Section: Discussionmentioning

confidence: 99%

“…Because of the elusive cause of OAVS and the substantial contribution of CNVs to genetic susceptibility of complex disorders, a genome-wide survey of genomic aberrations, including common and rare variants, might be used instead of a traditional genetic analysis. Recently, array studies indeed have confirmed the presence of microdeletions in some sporadic cases with features of OAVS (Ala-Mello et al 2008;Xu et al 2008;Rooryck et al 2009;Huang et al 2010). However, to our knowledge, a family-based association between CNVs and the OAVS phenotype has not been investigated.…”

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confidence: 93%

“…Maternal use of medications (Jacobsson and Granstrom 1997;Johnston and Bronsky 1995) and maternal diabetes (Wang et al 2002) contribute to infants with OAVS, which suggests that nongenetic factors play a role in the development of OAVS. Nevertheless, chromosomal aberrations (Engiz et al 2007;Balci et al 2006;Choong et al 2003;Descartes 2006;Josifova et al 2004;Ala-Mello et al 2008;Xu et al 2008;Rooryck et al 2009) and the identification of several families with autosomal dominant (Tsai and Tsai 1993;Stoll et al 1998;Tasse et al 2007;Goodin et al 2009;Vendramini-Pittoli and Kokitsu-Nakata 2009) or recessive inheritance (Kaye et al 1992) indicate that OAVS has a hereditary basis.…”

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confidence: 99%

“…In addition, a few patients showing clinical overlap with OAVS had mutations in sal-like 1 (SALL1) (Kohlhase et al 1999;Keegan et al 2001;Kosaki et al 2007) or Treacher Collins-Franceschetti syndrome 1 (TCOF1) (Su et al 2007), the genes responsible for most cases of Townes-Brocks syndrome [OMIM 107480] and Treacher Collins syndrome [OMIM 154500], respectively, which are also associated with first and second branchial arch anomalies. Even though cytogenetic alterations have been associated with many cases of OAVS, most of the chromosomal aberrations are patient-specific, except that chromosome 5p (Choong et al 2003;Descartes 2006;Josifova et al 2004;Ala-Mello et al 2008) and 22q (Balci et al 2006;Xu et al 2008;Derbent et al 2003;Digilio et al 2009) have been implicated in a number of cases.…”

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confidence: 99%

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Genome-Wide Scanning Reveals Complex Etiology of Oculo-Auriculo-Vertebral Spectrum

Huang

Tan

et al. 2010

Tohoku J. Exp. Med.

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Oculo-auriculo-vertebral spectrum (OAVS) is a common developmental disorder involving first and second pharyngeal arches. Although some family cases and such patients showing chromosomal aberrations suggest that OAVS have a genetic basis, no consistent genetic defects have been recorded at present time. Thus, we conducted genetic studies of a three-generation family with five OAVS patients to identify a causative variant for OAVS. Cytogenetic studies revealed those family members had a normal karyotype and no causative mutations were founded in SALL1 and TCOF1 , which known to be responsible for two other syndromes that have clinical overlapping with OAVS. Genotyping with commercially available BeadChips was performed on 13 individuals in the same family, showing no significant difference between the affected and normal members in terms of copy number variations (CNVs) in either number or size and no definitive causative CNV. A total of 8,224 informative autosomal SNPs that are evenly distributed throughout the genome were selected for both parametric and non-parametric linkage analysis. Significant negative LOD scores were obtained for the reported OAVS locus, providing further evidence for genetic heterogeneity of this complex disorder. The highest LOD score of 1.60 was noted on chromosome 15q26.2-q26.3 showing a potential linkage to this locus. The variable phenotypes of the affected members and the failure to identify a causative variant indicate that a complex etiology may be present even in a consanguineous family, which makes it more challenging to ascertain the cause of OAVS in further analysis.

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Section: Discussionmentioning

confidence: 99%

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confidence: 93%

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confidence: 99%

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confidence: 99%

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Genome-Wide Scanning Reveals Complex Etiology of Oculo-Auriculo-Vertebral Spectrum

Huang

Tan

et al. 2010

Tohoku J. Exp. Med.

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“…So far, only a small number of 'atypical deletions' [Kurahashi et al, 1996[Kurahashi et al, , 1997Garcia-Minaur et al, 2002;Rauch et al, 2005;D'Angelo et al, 2007;Fernandez et al, 2009] and 'distal deletions' [Rauch et al, 1999[Rauch et al, , 2005Saitta et al, 1999;Mikhail et al, 2007;Ben-Shachar et al, 2008;Rodningen et al, 2008;Xu et al, 2008;Bruce et al, 2009;Lafay-Cousin et al, 2009] were discovered. Here, we describe the case of a 5-year-old girl with an atypical and distal 22q11.2 deletion slightly overlapping with the 3-Mb recurrent deletion and compare the clinical features of our case with those reported in the literature.…”

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confidence: 99%

22q11.2 Distal Deletion Syndrome: Description of a New Case with Truncus Arteriosus Type 2 and Review

et al. 2011

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22q11.2 deletion syndrome is mainly characterized by conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial appearance. The etiology in the majority of patients is a 3-Mb recurrent deletion in region 22q11.2. Nevertheless, recently some cases of infrequent deletions with various sizes have been reported with a different phenotype. We report on a patient with congenital heart disease (truncus arteriosus type 2) in whom a de novo 1.3-Mb 22q11.2 deletion was detected by array comparative genomic hybridization. The deletion described corresponds to an atypical and distal deletion which spans low copy repeat (LCR) 4 and is associated with breakpoint sites that do not correspond to known LCRs of 22q11.2. We examine the clinical phenotype of our case and compare our findings with those published in the literature. The most prevalent clinical features in this type of deletion are a history of prematurity, pre-natal and post-natal growth retardation, slight facial dysmorphic features, microcephaly and developmental delay, with a speech defect in particular. These are clearly different from those found in the classic 22q11.2 deletion syndrome, and we believe that the main differential diagnosis should be with Silver-Russel syndrome. In our case we observe the cardiac phenotype with truncus arteriosus communis usually seen in the classic 22q11.2 deletion syndrome, and so far associated with the TBX1 gene. Significantly, however, TBX1 is not included in our patient’s deletion. The possible roles of a position effect or other genes are discussed.

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Three patients with oculo‐auriculo‐vertebral spectrum and microdeletion 22q11.2

Digilio

McDonald‐McGinn

Heike

et al. 2009

American J of Med Genetics Pt A

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We report on three unrelated patients with the 22q11.2 microdeletion syndrome (del22q11) who have phenotypic anomalies compatible with oculo-auriculo-vertebral spectrum (OAVS). Hemifacial microsomia, unilateral microtia, hearing loss, congenital heart/aortic arch arteries defects, and feeding difficulties were present in all three patients. Additional anomalies occasionally diagnosed included coloboma of the upper eyelid, microphthalmia, cerebral malformation, palatal anomalies, neonatal hypocalcemia, developmental delay, and laryngomalacia. Several clinical features characteristic of OAVS have been described in patients with del22q11 from the literature, including ear anomalies, hearing loss, cervical vertebral malformations, conotruncal cardiac defects, renal malformations, feeding and respiratory difficulties. Atretic ear with facial asymmetry has been previously described in one patient. Thus, clinical expression of hemifacial microsomia and microtia resembling OAVS should now be included within the wide phenotypic expression of del22q11. The occurrence of this manifestation in del22q11 is currently low. Nevertheless, patients with hemifacial microsomia and microtia associated with clinical features typically associated with del22q11 should now have for specific cytogenetic testing.

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A child with features of Goldenhar syndrome and a novel 1.12 Mb deletion in 22q11.2 by cytogenetics and oligonucleotide array CGH: Is this a candidate region for the syndrome?

Cited by 53 publications

References 12 publications

Genome-Wide Scanning Reveals Complex Etiology of Oculo-Auriculo-Vertebral Spectrum

Genome-Wide Scanning Reveals Complex Etiology of Oculo-Auriculo-Vertebral Spectrum

22q11.2 Distal Deletion Syndrome: Description of a New Case with Truncus Arteriosus Type 2 and Review

Three patients with oculo‐auriculo‐vertebral spectrum and microdeletion 22q11.2

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