Family Collection, Phenotype Analysis And Genetic Study Of Goldenhar Syndrome

Objective To analyze the clinical phenotype and apply the referenced diagnose for Goldenhar syndrome; To collect the genetic resourse of Goldenhar syndrome for providing us with the information to explore etiological factors for this disorder.Methods A series of 69 patients with Goldenhar syndrome were retrospectively reviewed, and Pearson's correlation analysis were performed. and their unaffected parents were collected with genome DNA. Genomic DNA was extracted from peripheral blood samples of the members of a family with Goldenahr syndrome and another four family Trios (father, mother and patient) using a genomic DNA purification kit.Results Of the 69 patients with Goldenhar syndrome, Most cases (91.3%) were sporadic, and 34 patients were male and 35 patients were female, Bilateral involvement was present in 39 cases (56.5%), whereas 30 cases (43.5%,14 showed on the left side and 16 on the right side) were unilateral affected. Preauricular tag (88.4%), epibulbar dermoids (84.1%) and other anomalies of the eyes (52.2%) were mail clinical signs, and hemifacial microsomia correlated with orofacial cleft, dysplasia of maxilla and/or mandible, and anomalies of the ears, other than malformed auricle and preauricular tag (p<0.05). Dysnoesia clustered with brain anomalies, visual deterioration, delay of speech development, and anomalies of the ears, other than malformed auricle and preauricular tag (p<0.01). A family with 5 Goldenhar syndrome patients and the Trios families of 4 sporadic cases were collected with genomic DNA.Conclusion Goldenhar syndrome is a complex condition and shows variable phenotypes, and some clinical signs belonging to the associated developmental fields often appeared together. Patients with bilateral involvement often suffered more developmental abnormalities and required more careful examinations. The genetic resource of one family with Goldenhar syndrome and another 4 Trios families were collected for providing us with the information to reveal the aetiology mechanism of this disorder. Objective Mutation screen of SALL1 and TCOF1 in eight patients with Goldenhar syndrome to explore the pathogenic cause of this complex disorder.Methods eight patients and their unaffected relatives were collected with clinical data and genome DNA. All the exons and some of the introns of SALL1 and TCOF1 were amplified by polymerase chain reaction (PCR) and the PCR products were subjected to autotic DNA sequencing.Results Two polymorphic sites in SALL1 and seven variants in TCOF1 were detected, and all the variants also presented in the unaffected individuals, showing no mutation segregating with the disease.Conclusion Pathogenic mutation of SALL1 and TCOF1 were excluded in these patients, supporting that Goldenhar syndrome is a specific entity. Objective Investigate the copy number variations (CNVs) in a family with Goldenhar syndrome and four sporadic patients to identify possible susceptibility locus.Methods Genomic DNA of 13 family members and 4 family Trios(father, mother and patient) was genotyped with Illumina Human 370 Genotyping BeadChip. Results were analyzed using Beadstudio software to identify CNVs. Then, one de novo CNV region which may be associated with the disorder was validated by real-time PCR.Results Ten de novo CNVs were identified in 3 sporadic patients. After analyzing the information of database of genomic variants (DGV), CNVs of 27 health controls and all the genes in the 10 CNV regions, three CNVs located on 5q13.2,1q31.1 and 8p23.1 may be considered to associate with Goldenhar syndrome. Then, the CNV on 5q13.2 was confirmed by real-time PCR. A total of 153 CNVs were identified in the family with 5 Goldenhar syndrome patients, but there were no significant differences of the CNV number (p=0.649, t-test) or CNV size (p=0.304, Wilcoxon Mann-Whitney test) between the affected and unaffected individuals, and no clear copy number variation was identified responsible for Goldenhar syndrome in this family.Conclusion A microdeletion in 5q13.2, a microreplication in 1q31.1 and a microdeletion in 8p23.1 may be associated with Goldenhar syndrome. CNV analysis in the family identified no causative variant, indicating that a complex aetiology may be present even in a consanguineous family, which makes the ascertainment of the cause of Goldenhar syndrome challenging.