Combining RSPH9 founder mutation screening and next-generation sequencing analysis is efficient for primary ciliary dyskinesia diagnosis in Saudi patients.

Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous ciliopathy. Dysfunction of motile respiratory and nodal cilia results in sinopulmonary symptoms associated with laterality defects (LD) found in half of the patients. The molecular basis of the disease is insufficiently investigated in patients originating from the Arabian Peninsula. In a group of 16 unrelated Saudi patients clinically suspected of PCD and among whom only 5 (31%) had LD, we first screened by PCR-RFLP two founder mutations, RSPH9 c.804_806del and CCDC39 c.2190del previously identified in patients from the Arabian Peninsula and Tunisia, respectively. When negative, targeted panel or whole-exome sequencing was performed. Three patients were homozygous for the mutation in RSPH9, which encodes an axonemal protein that is absent from nodal cilia. None of the patients carried the CCDC39 founder mutation frequent in Tunisia. NGS analysis showed that nine patients had homozygous mutations in PCD genes. In total, sequential RFLP and NGS analysis solved 75% (12/16) of cases and identified ten distinct mutations, among which six are novel, in nine different genes. These results, which highlight the genetic heterogeneity of PCD in Saudi Arabia, show that the RSPH9 c.804_806del mutation is a prevalent mutation among Saudi patients, whereas the CCDC39 c.2190del ancestral allele is most likely related to the Berber population. This study shows that RSPH9 founder mutation first-line screening and NGS analysis is efficient for the genetic exploration of PCD in Saudi patients. The RSPH9 founder mutation accounts for the low rate of LD among Saudi patients.

Childhood tuberculosis: A descriptive study in a pneumo-pediatrics department in Tunisia.

Objective to assess the different localizations of tuberculosis (TB) in children in a pneumopediatric department in Tunisia and to describe its diagnosis tools since clinical investigations of childhood TB are challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. Methods Forty-six cases of TB in children were studied between 2008 and 2013. Clinical history, examination and chest radiography were reported. Several investigations have been conducted to confirm the diagnosis of TB such as: tuberculin skin test (TST), bacteriological and histological investigations. Anti-tuberculosis treatment was prescribed according to the national guidelines. Results Cough and deterioration in general condition were the most frequent symptoms (47.8% and 43.7%). The other children presented cervical swelling (19.5%), chest pain (17.4%) and hemoptysis (4.3%). Abnormalities have been found in chest radiography in 35 cases (76%). TST was positive in 73% of cases. Diagnosis of TB was confirmed in 56.6% of cases by Mycobacterium tuberculosis (MT) isolation and/or biopsy. The diagnosis was made on presumptive arguments in 20 cases (43.4%) based on a history of TB contact, suggestive symptoms and a positive TST. A surgical biopsy was necessary for diagnosis in 17 cases (nasopharynx, bone, cervical, mediastinal and mesenteric lymph nodes). Pulmonary TB was diagnosed in 52% of cases. Two children were diagnosed with disseminated TB. A diagnosis delay was noted with an average of 20 days and a contact history was found in 52% of the children. All children were treated according to the national guidelines without major side effects. Healing without sequelae was achieved in 91% of cases. Conclusion Children represent a population at high risk for TB especially after a household contact with a higher frequency of multifocal forms compared to adults. The difficulty of the diagnosis in children may explain partially the diagnosis delay, but efforts must be done to improve prevention and diagnosis in our country.