| #613091 | ||||||||||
| ASPHYXIATING THORACIC DYSTROPHY 3; ATD3 | ||||||||||
| Phenotype Gene Relationships | ||||||||||
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| Phenotypic Series | ||||||||||
| TEXT | ||||||||||
| A number sign (#) is used with this entry because of evidence that ATD3 is caused by homozygous or compound heterozygous mutation in the DYNC2H1 gene (603297) on chromosome 11q14.3-q23.1. For a general phenotypic description and a discussion of genetic heterogeneity of asphyxiating thoracic dystrophy, also known as Jeune syndrome, see 208500. | ||||||||||
| Clinical Features | ||||||||||
| Through a study to identify the molecular basis of asphyxiating thoracic dystrophy (ATD) and the related but more severe disorder short rib-polydactyly syndrome (see 263530), Dagoneau et al. (2009) identified 3 families with ATD. Criteria for inclusion in the study were short ribs and a restricted thoracic cage; trident acetabular roof; small hands and feet; and shortening of the long bones. The 3 families with ATD were a large consanguineous Moroccan family and 2 small nonconsanguineous families from France. The 3 ATD families included 5 cases. In the first family, one child died of respiratory distress, and pregnancy of her aunt was terminated at 28 weeks' gestation for severe narrowing of the thorax. In the second family, 2 pregnancies were terminated for severe narrowing of the thorax. In the third family the affected child was 19 years old at the time of the report; no eye, liver, or kidney manifestations were detected. | ||||||||||
| Mapping | ||||||||||
| Using linkage and microsatellite marker analysis in a large consanguineous Moroccan family, Dagoneau et al. (2009) mapped the ATD phenotype to chromosome 11q14.3-q23.1, in a 20.4-Mb region bounded centomerically by D11S4175 and telomerically by D11S1893. The region contains 85 genes. | ||||||||||
| Molecular Genetics | ||||||||||
| Among the genes in the 20.4-Mb critical region for ATD, Dagoneau et al. (2009) considered DYNC2H1 a good candidate gene because it encodes a subunit of a cytoplasmic dynein complex. The authors sequenced all 90 exons of the DYNC2H1 gene and identified 2 homozygous missense mutations in the 2 affected Moroccan children (M1991L, 603297.0001 and M3762V, 603297.0002). The mutations cosegregated with the disease and were not identified in 210 ethnically matched control chromosomes. Dagoneau et al. (2009) identified 4 other missense and nonsense mutations in compound heterozygosity in 2 other families, both nonconsanguineous, with ATD. | ||||||||||
| REFERENCES | ||||||||||
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