Quantitative analysis of limb anomalies in CHARGE syndrome: Correlation with diagnosis and characteristic CHARGE anomalies

Brock, Katharine E.; Mathiason, Michelle A.; Rooney, Brenda L.; Williams, Marc S.

doi:10.1002/ajmg.a.20526

Cited by 21 publications

(18 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, the presence of choanal atresia together with ear defects and developmental delay points to an overlap between CHARGE and Okihiro syndromes. Since limb malformations do occur in CHARGE syndrome (Brock et al, 2003), contiguous gene deletions including SALL4 should be considered in cases diagnosed with CHARGE syndrome but without CHD7 mutation. Physical features not reported with SALL4 defects.…”

Section: Discussionmentioning

confidence: 99%

Multigene deletions on chromosome 20q13.13-q13.2 includingSALL4 result in an expanded phenotype of Okihiro syndrome plus developmental delay

et al. 2007

View full text Add to dashboard Cite

Okihiro syndrome results from truncating mutations in the SALL4 locus on the chromosome 20q13.13-q13.2. Deletions of the whole SALL4 coding region as well as single exon deletions are also a common cause of Okihiro syndrome and indicate haploinsufficiency as the disease causing mechanism. The phenotypes caused by SALL4 deletions are not different from those caused by point mutations. No multigene deletion including SALL4 has been documented to date. Here we report the detection and molecular characterization of four novel, overlapping microdeletions, all spanning SALL4 and flanking genes, in four unrelated cases with features of Okihiro syndrome and variable degrees of psychomotor delay. All deletions were first identified and mapped by quantitative Real Time PCR. Subsequently, three of four deletions were mapped in further detail by high-resolution array CGH (244k oligo-arrays). All cases had larger deletions of varying size (1.76-1.78 Mb, 2.01-2.05 Mb, 2.16-2.17 Mb, and 1.3-2.8 Mb, respectively), which included SALL4 plus 3 to 7 additional functional genes. While three cases with largely overlapping deletions are mildly developmentally delayed, the only patient with a more centromeric deletion is clearly mentally retarded. In this patient, four genes (MOCS3, DPM1, ADNP, BCAS4) are deleted, which were not affected in the other three cases, suggesting that the deletion of one or more of these genes contributes to the mental retardation. Since two of the four cases presented with choanal atresia, large deletions including SALL4 should be considered in the differential diagnosis of children with suspected CHARGE syndrome but without detectable CHD7 mutations.

show abstract

Section: Discussionmentioning

confidence: 99%

Multigene deletions on chromosome 20q13.13-q13.2 includingSALL4 result in an expanded phenotype of Okihiro syndrome plus developmental delay

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Historically, limb involvement did not receive much attention in CHARGE until Brock et al [2003] studied in depth that aspect of the disorder and showed that limb involvement occurs in over onethird of CHARGE patients. This frequency is higher than that observed for other more familiar features such as esophageal atresia, part of the new diagnostic criteria proposed by Verloes [2005], so we propose that the ''E'' should expand to reflect involvement of extremities.…”

mentioning

confidence: 98%

Expanding the “E” in CHARGE

Alazami

Alzahrani

Alkuraya

2008

American J of Med Genetics Pt A

View full text Add to dashboard Cite

“…Recently, limb anomalies have been reported as a rare manifestation in CHARGE syndrome [3,17,19]. On the other hand, Brock et al [4] reported that limb anomalies occurred in about 30% of patients with definite or probable CHARGE syndrome. It is interesting that limb anomalies with DiGeorge sequence are more frequently observed in male (P value <0.034), and limb anomalies were observed in 70.0% of male DiGeorge sequence with definite CHARGE syndrome [4].…”

Section: Discussionmentioning

confidence: 96%

“…Limb anomalies were not initially described in CHARGE syndrome [4]. Recently, limb anomalies have been reported as a rare manifestation in CHARGE syndrome [3,17,19].…”

Section: Discussionmentioning

confidence: 97%

“…On the other hand, Brock et al [4] reported that limb anomalies occurred in about 30% of patients with definite or probable CHARGE syndrome. It is interesting that limb anomalies with DiGeorge sequence are more frequently observed in male (P value <0.034), and limb anomalies were observed in 70.0% of male DiGeorge sequence with definite CHARGE syndrome [4]. Williams proposed that CHARGE syndrome is caused by a disruption of mesenchymal-epithelial (including ectoderm and endoderm) interaction [27].…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism

et al. 2010

View full text Add to dashboard Cite

It is rare that coloboma, heart anomalies, choanal atresia, retarded growth and development, and genital and ear anomalies (CHARGE) syndrome patients have DiGeorge sequence showing severe immunodeficiency due to the defect of the thymus. Although the only treatment to achieve immunological recovery for these patients in countries where thymic transplantation is not ethically approved would be hematopoietic cell transplantation, long-term survival has not been obtained in most patients. On the other hand, it is still not clarified whether hypoparathyroidism is one of the manifestations of CHARGE syndrome. We observed a CHARGE syndrome patient with chromodomain helicase DNA-binding protein 7 mutation showing DiGeorge sequence including the defect of T cells accompanied with the aplasia of the thymus, severe hypoparathyroidism, and conotruncal cardiac anomaly. He received unrelated cord blood transplantation without conditioning at 4 months of age. Recovery of T cell number and of proliferative response against mitogens was achieved by peripheral expansion of mature T cells in cord blood without thymic output. Although he is still suffering from severe hypoparathyroidism, he is alive without serious infections for 10 months.

show abstract

Quantitative analysis of limb anomalies in CHARGE syndrome: Correlation with diagnosis and characteristic CHARGE anomalies

Cited by 21 publications

References 68 publications

Multigene deletions on chromosome 20q13.13-q13.2 includingSALL4 result in an expanded phenotype of Okihiro syndrome plus developmental delay

Multigene deletions on chromosome 20q13.13-q13.2 includingSALL4 result in an expanded phenotype of Okihiro syndrome plus developmental delay

Expanding the “E” in CHARGE

Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism

Contact Info

Product

Resources

About