A novel deletion variant in CLN3 with highly variable expressivity is responsible for juvenile neuronal ceroid lipofuscinoses.

Mutations in CLN3 (OMIM: 607042) are associated with juvenile neuronal ceroid lipofuscinoses (JNCL)-a rare neurodegenerative disease with early retinal degeneration and progressive neurologic deterioration. The study aimed to determine the underlying genetic factors justifying the NCL phenotype in a large Iraqi consanguineous family. Four affected individuals with an initial diagnosis of NCL were recruited. By doing neuroimaging and also pertinent clinical examinations, e.g. fundus examination, due to heterogeneity of neurodevelopmental disorders, the proband was subjected to the paired-end whole-exome sequencing to identify underlying genetic factors. The candidate variant was also confirmed by Sanger sequencing. Various in silico predictions were used to show the pathogenicity of the variant. This study revealed a novel homozygous frameshift variant-NM_000086.2: c.1127del; p.(Leu376Argfs*15)-in the exon 14 of the CLN3 gene as the most likely disease-causing variant. Three out of 4 patients showed bilateral vision loss (< 7 years) and retinal degeneration with macular changes in both eyes. Electroencephalography demonstrated the loss of normal posterior alpha rhythm and also low amplitude multifocal slow waves. Brain magnetic resonance imaging of the patients with a high degree of deterioration showed mild cerebral and cerebellar cortical atrophy, mild ventriculomegaly, thinning of the corpus callosum and vermis, and non-specific periventricular white matter signal changes in the occipital area. The novel biallelic deletion variant of CLN3 was identified that most probably led to JNCL with variable expressivity of the phenotype. This study also expanded our understanding of the clinical and genetic spectrum of JNCL.

Misleading of the diagnosis of Mycobacterium attributed lung diseases to malignancy due to smear, culture and PCR negative results: A lesson from a case report.

The incidence of non-tuberculous mycobacteria (NTM) attributed diseases are rising and they are responsible for an increasing proportion of mycobacterial diseases, worldwide. However, their diagnosis is still a big challenge. In this study, a 77-year-old diabetic woman with familial history of lung cancer and 40 pack/year smoking history was presented. She described significant weight loss, shortness of breath, yellow productive sputum, fever, and chills from 4 months ago. The empirical antibiotic therapy didn't cause a significant improvement in the patient's health condition. Also, the sputum smear, culture, and polymerase chain reaction-based (PCR) tests were negative for Mycobacterium tuberculosis (MTB). Computed tomography scanning identified a consolidation at the right upper lobe which was susceptible to malignancy. Non-caseous granulomatous inflammation with the presence of acid-fast bacillus was detected in the biopsies. Therefore, the patient's sputum was reexamined. Although PCR was negative, both smear and culture became positive. PCR-based amplification of a 596 bp fragment of 16S rRNA gene of the isolated bacteria, followed by almost full 16S rRNA sequencing, identified the Mycobacterium fortuitum strain. No malignant cell was detected at pathology evaluations. Due to the increase of NTM attributed diseases which can exhibit negative PCR for MTB and low reliability of negative results of sputum smear and culture, multiple repetitions of the sputum evaluations and, utilizing from 16S rRNA sequencing is recommended to diagnose NTM related lung disease.