Juberg-Hayward syndrome is a cohesinopathy, caused by mutation in ESCO2
| Autor: | Chumpol Ngamphiw, Suttichai Krisanaprakornkit, Bjorn R. Olsen, Sissades Tongsima, Jame R Ketudat Cairns, Worrachet Intachai, Katsushige Kawasaki, Atsushi Ohazama, Prapai Dejkhamron, Piranit Nik Kantaputra |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microcephaly Clinodactyly Cohesin complex Chromosomal Proteins Non-Histone Cleft Lip Orthodontics Short stature Mice 03 medical and health sciences Ptosis Acetyltransferases medicine Animals Humans Exome sequencing 030102 biochemistry & molecular biology business.industry Anatomy Orofaciodigital Syndromes Synostosis medicine.disease Cleft Palate 030104 developmental biology Mutation Juberg Hayward syndrome medicine.symptom business |
| Zdroj: | European Journal of Orthodontics. 43:45-50 |
| ISSN: | 1460-2210 0141-5387 |
| DOI: | 10.1093/ejo/cjaa023 |
| Popis: | Summary Background Juberg-Hayward syndrome (JHS; MIM 216100) is a rare autosomal recessive malformation syndrome, characterized by cleft lip/palate, microcephaly, ptosis, short stature, hypoplasia or aplasia of thumbs, and dislocation of radial head and fusion of humerus and radius leading to elbow restriction. Objective To report for the first time the molecular aetiology of JHS. Patient and methods Clinical and radiographic examination, whole exome sequencing, Sanger sequencing, mutant protein model construction, and in situ hybridization of Esco2 expression in mouse embryos were performed. Results Clinical findings of the patient consisted of repaired cleft lip/palate, microcephaly, ptosis, short stature, delayed bone age, hypoplastic fingers and thumbs, clinodactyly of the fifth fingers, and humeroradial synostosis leading to elbow restriction. Intelligence is normal. Whole exome sequencing of the whole family showed a novel homozygous base substitution c.1654C>T in ESCO2 of the proband. The sister was homozygous for the wildtype variant. Parents were heterozygous for the mutation. The mutation is predicted to cause premature stop codon p.Arg552Ter. Mutations in ESCO2, a gene involved in cohesin complex formation, are known to cause Roberts/SC phocomelia syndrome. Roberts/SC phocomelia syndrome and JHS share similar clinical findings, including autosomal recessive inheritance, short stature, cleft lip/palate, severe upper limb anomalies, and hypoplastic digits. Esco2 expression during the early development of lip, palate, eyelid, digits, upper limb, and lower limb and truncated protein model are consistent with the defect. Conclusions Our study showed that Roberts/SC phocomelia syndrome and JHS are allelic and distinct entities. This is the first report demonstrating that mutation in ESCO2 causes JHS, a cohesinopathy. |
| Databáze: | OpenAIRE |
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