Article Text

other Versions

PDF
Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia
  1. Nadejda Maksimova (nogan{at}yandex.ru)
  1. Yakut Scientific Center of Russian Academy of Medical Sciences and Government of the RS(Y), Russian Federation
    1. Kenju Hara (hara{at}bri.niigata-u.ac.jp)
    1. Brain Reseacr Institute, Japan
      1. Akinori Miyashita
      1. Genome Science Branch, Center for Bioresource-Based Researches, Brain Research Institute, Niigata U, Japan
        1. Irina Nikolaeva
        1. Yakut Scientific Centre of Russian Academy of Medical Sciences and Government of Republic of Sakha (, Russian Federation
          1. Atsushi Shiga (shiga{at}bri.niigata-u.ac.jp)
          1. Department of Neurology, Brain Research Institute, Niigata University, Japan
            1. Anna Nogovicina
            1. Republican Hospital & National Medical Centre, Yakutsk, Russian Federation
              1. Aitalina Sukhomyasova
              1. Republican Hospital & National Medical Centre, Russian Federation
                1. Valery Argunov
                1. Yakut Scientific Centre of Russian Academy of Medical Sciences and Government of Republic of Sakha, Russian Federation
                  1. Anna Shvedova
                  1. Republican Hospital & National Medical Centre, Russian Federation
                    1. Takeshi Ikeuchi
                    1. Department of Molecular Neuroscience, Resource Branch for Brain Disease, Brain Research Institute, Japan
                      1. Masatoyo Nishizawa
                      1. Department of Neurology, Brain Research Institute, Niigata University, Japan
                        1. Ryozo Kuwano
                        1. Genome Science Branch, Center for Bioresource-Based Researches, Brain Research Institute, Niigata Un, Japan
                          1. Osamu Onodera (onodera{at}bri.niigata-u.ac.jp)
                          1. Brain Research Institute, Niigata University, Japan

                            Abstract

                            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
                            • CUL7
                            • Yakuts
                            • neonatal respiratory distress
                            • vasularization

                            Statistics from Altmetric.com

                            Request permissions

                            If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.