Background: We have identified 43 patients having short stature syndrome in 37 Yakut families with autosomal recessive pre- and postnatal nonprogressive growth failure and facial dysmorphism but with normal intelligence.
Methods: Because Yakuts are considered as a population isolate and the disease is rare in other populations, we performed a genomewide homozygosity mapping using 763 microsatellite markers and candidate gene approach in the critical region to identify the causative gene for the short stature syndrome in Yakut.
Results: we revealed that all families shared the identical haplotype in the region to the identical loci responsible for 3-M syndrome and gloomy face syndrome and found a novel homozygous 4582insT mutation in Cullin 7 (CUL7), which resulted in a frameshift mutation and the formation of a subsequent premature stop codon at 1553 (Q1553X). The Yakut patients with short stature syndrome have unique phenotypes such as a high frequency of neonatal respiratory distress and few bone abnormalities, whereas the other clinical features of the Yakut patients were similar to those of 3-M syndrome. Furthermore, we showed an abnormal vascularization in the fetal placenta and an abnormal development of cartilage tissue in the bronchus of the one fetus with CUL7 mutation.
Conclusion: These findings may provide a new understanding of the clinical diversity and pathogenesis of short stature syndrome with CUL7 mutation.
- 3-M syndrome
- neonatal respiratory distress
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