Novel STAG1 Frameshift Mutation in a Patient Affected by a Syndromic Form of Neurodevelopmental Disorder.

The cohesin complex is a large evolutionary conserved functional unit which plays an essential role in DNA repair and replication, chromosome segregation and gene expression. It consists of four core proteins, SMC1A, SMC3, RAD21, and STAG1/2, and by proteins regulating the interaction between the complex and the chromosomes. Mutations in the genes coding for these proteins have been demonstrated to cause multisystem developmental disorders known as "cohesinopathies". The most frequent and well recognized among these distinctive clinical conditions are the Cornelia de Lange syndrome (CdLS, OMIM 122470) and Roberts syndrome (OMIM 268300). STAG1 belongs to the STAG subunit of the core cohesin complex, along with five other subunits. Pathogenic variants in STAG1 gene have recently been reported to cause an emerging syndromic form of neurodevelopmental disorder that is to date poorly characterized. Here, we describe a 5 year old female patient with neurodevelopmental delay, mild intellectual disability, dysmorphic features and congenital anomalies, in which next generation sequencing analysis allowed us to identify a novel pathogenic variation c.2769_2770del p.(Ile924Serfs*8) in STAG1 gene, which result to be de novo. The variant has never been reported before in medical literature and is absent in public databases. Thus, it is useful to expand the molecular spectrum of clinically relevant alterations of STAG1 and their phenotypic consequences.

Low frequency of axial involvement in southern Italian Caucasian children with HLA-B27 positive juvenile onset undifferentiated spondyloarthritis.

OBJECTIVES: To establish how many children with HLA B27-positive juvenile undifferentiated spondyloarthritis (JuSpA) living in southern Italy develop axial disease after 5 years of disease. METHODS: All children with B27-positive enthesitis-related arthritis (ERA) consecutively seen in a 7-year period were entered in a special register and were followed prospectively. Each patient was examined at 6-month intervals, even if asymptomatic. In patients with inflammatory spinal pain and/or buttock pain, MRI of the sacroiliac joints and spine was performed. Five years after inclusion, sacroiliac joint plain radiographs were obtained and read blindly after being mixed with those of control subjects. RESULTS: Thirteen children, 9 boys and 4 girls, with B27-positive ERA and one girl with B27-positive isolated SpA dactylitis were seen in the study period. Their median age at disease onset and at our first examination were 10 (range 2-16) and 12 years (range 3-16), respectively. During follow-up, only one patient had axial symptoms, i.e. alternate buttock pain. MRI revealed moderate bone oedema at both sacroiliac joints. After five years of disease, no patient showed reduced spinal movement. No sign of sacroiliitis was seen in any patient and control on plain films. A new MRI of the sacroiliac joints of the patient who showed bone oedema in the first years of disease was normal. CONCLUSIONS: This study confirms that the onset of axial involvement in Italian Caucasian HLA-B27 positive children with ERA is rare in the first five years of disease.

Cystic fibrosis presenting as metabolic alkalosis in a boy with the rare D579G mutation.

We report on a 10-month-old boy with hypotonic dehydration and metabolic alkalosis. Sweat test was borderline and genetic analysis was negative for common mutations. Analysis of the whole coding regions of the CFTR gene revealed the rare mutation D579G in homozygosity.