Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia

• Published in: Journal of Medical Genetics
• Main Authors: Maksimova, Nadejda, Hara, Kenju, Miyashita, Akinori, Nikolaeva, Irina, Shiga, Atsushi, Nogovicina, Anna, Sukhomyasova, Aitalina, Argunov, Valery, Shvedova, Anna, Ikeuchi, Takeshi, Nishizawa, Masatoyo, Kuwano, Ryozo, Onodera, Osamu
• Format: Text
• Language: English
• Published: British Medical Journal Publishing Group 2007
• Subjects: Original articles; Yakuts
• Online Access: http://jmg.bmj.com/cgi/content/short/jmg.2007.051979v1; https://doi.org/10.1136/jmg.2007.051979

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.