A novel de novo mutation in the PURA gene associated with a new clinical finding: large brainstem

We report the case of a Caucasian Spanish boy, who showed profound neonatal hypotonia, feeding difficulties, apnea, severe developmental delay, epilepsy, bilateral convergent strabismus, poor verbal language development and a large brainstem. Whole-exome sequence uncovered a novel de novo mutation in the purine-rich element binding protein A gene (PURA; NM_005859.4:c.72del:p.(- Gly25AlafsTer53)) that encodes the transcriptional activator protein Pur-alpha (PURA). Mutations in this gene have been identified in patients with PURA syndrome, a rare disorder characterized by an early hypotonia, developmental delay, severe intellectual disability with or without epilepsy, and disability in expressive language development. Although, up to 75 cases have been identified worldwide, to the best of our knowledge, this is the first patient described with a brainstem larger than normal. In conclusion, our data expand both genetic and phenotypic spectrum associated with PURA gene mutations.

Screening of familial primary biliary cholangitis and research on low-frequency mutations by whole-exome sequencing / 中华肝脏病杂志

Objective@#Screening of patients with familial primary biliary cholangitis by using whole-exome sequence to find common low-frequency mutations and to explore its pathogenesis. @*Methods@#The confirmed data of PBC patients diagnosed in Xijing hospital from 2005 to 2016 were collected, and their first-degree relatives' autoantibodies were screened for diagnosis. DNA extraction from PBC patients and normal controls in two high-incidence families was performed for whole-exome sequencing, and the low-frequency mutations in the family were screened. @*Results@#A total of 435 PBC patients and 946 first-degree relatives were screened, and 18 (1.90%) first-degree relatives were also diagnosed with PBC, which was distributed in 16 families (3.68%). The whole-exome sequencing results showed that the common low-frequency mutations of 7 patients in 2 families consisted of 16 single nucleotide polymorphisms and 2 InDel markers, of which ANO2(rs17788563) may be correlated to the pathogenesis of PBC. @*Conclusion@#There is high-incidence of PBC in the family members of PBC patients with low-frequency mutation sites and their sites may be involved in the pathogenesis of PBC.

Disease genes detection of two anterior segment dysgenesis pedigree by whole exome sequence / 眼科新进展

Objective To identify the disease-causing gene mutation in families with anterior segment dysgenesis (ASD).Methods Two ASD families coming from Henan and Hebei provinces were enrolled in this study.Ocular examinations were performed,and periphery blood specimens were collected from each family member under the informed consent.The blood samples of 2 patients and 1 normal person in family 1 and 1 patient and 1 normal person in family 2 were analyzed by the whole exome sequences.The candidate genes were verified by Sanger sequence and predicted damages by PolyPhen-2 and SIFT Human Splicing Finder software.Results Family 1 including 9 patients were examined in serial 3 passages,which conformed to autosomal dominant inheritance pattern.Clinical examination revealed binocular anterior segment dysgenesis in the 9 patients.There were 13 SNV and 55 InDel candidate mutations.And missense mutation c.T2A(p.M1K)on PAX6 gene was found.Family 2 included 8 members,and 2 patients were examined.The splicing mutation c.357 + 1g ＞ c on the same gene was found.Conclusion T2A(p.M1 K) and c.357 + 1 g ＞ c mutations in PAX6 gene are responsible for ASD.Whole exome sequence provides a new approach to detect diseasecausing mutation of ASD with diversity clinical phenotypes.