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Asphyxiating thoracic dysplasia: clinical and molecular review of 39 families.
MedLine Citation:
PMID:  23339108     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Asphyxiating Thoracic Dysplasia (ATD) belongs to the short rib polydactyly group and is characterized by a narrow thorax, short long bones and trident acetabular roof. Other reported features include polydactyly, renal, liver and retinal involvement. To date, mutations in IFT80, DYNC2H1, TTC21B and WDR19 have been reported in ATD. The clinical and molecular heterogeneity leads to difficulties in the evaluation of the long-term prognosis.
METHODS: We investigated 53 ATD cases (23 living cases and 30 fetuses) from 39 families. They benefited from a combined approach of deep phenotyping and IFT80 and DYNC2H1 molecular screening.
RESULTS: Among the 23 postnatal cases, pulmonary insufficiency was noted in 60% of cases, with tracheotomy requirement in five cases. Renal and liver diseases occurred respectively in 17% and 22% of cases, whereas retinal alteration was present in 50% of cases aged more than 5 years. We identified DYNC2H1 mutations in 23 families (59%) and IFT80 mutations in two families (5%). However, in six families, only one heterozygote mutation in either IFT80 or DYNC2H1 was identified. Finally, the two genes were excluded in 14 families (36%).
CONCLUSIONS: We conclude that DYNC2H1 is a major gene responsible for ATD, while IFT80 is rarely involved. The presence of only one mutation in six families and the exclusion of the two genes in 14 families support the involvement of other causal cilia genes. The long-term follow up emphasizes that the pulmonary prognosis is probably less pejorative and retinal involvement more frequent than previously thought.
Authors:
Geneviève Baujat; Céline Huber; Joyce El Hokayem; Roseline Caumes; Claire Do Ngoc Thanh; Albert David; Anne-Lise Delezoide; Anne Dieux-Coeslier; Brigitte Estournet; Christine Francannet; Honorine Kayirangwa; Florence Lacaille; Muriel Le Bourgeois; Jelena Martinovic; Rémi Salomon; Sabine Sigaudy; Valérie Malan; Arnold Munnich; Martine Le Merrer; Kim Hanh Le Quan Sang; Valérie Cormier-Daire
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medical genetics     Volume:  50     ISSN:  1468-6244     ISO Abbreviation:  J. Med. Genet.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985087R     Medline TA:  J Med Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  91-8     Citation Subset:  IM    
Affiliation:
Department of Genetics, Paris Descartes-Sorbonne Paris Cité, Fondation Imagine, Hopital Necker-Enfants malades, AP-HP, U781, Paris 75015, France; valerie.cormier-daire@inserm.fr.
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