The Lung Mass and Nodule: A Case Series The Lung Mass and Nodule

Lung mass is an abnormal region of 3 cm or more in size present in the lungs mainly due to underlying pulmonary caner. It is usually round, opaque and poorly differentiated on X-ray. Common etiological key players are smoking, exposure to asbestos, radon, however, familial history may also play a role. We presented retrospectively7 cases of lung mass and nodule encountered during our clinical practice. We have discussed their clinical presentation, manifestation, medical history, radiological findings and differential diagnosis. In this case series, most of the patients were young, only 2 cases were older patients. There was one infant one month old, one female child 12 years old, one female 25 years, 2 males, 22 and 21 years, one male of 50 years and another male of 60 years age. Correct diagnosis on the basis of clinical profile, radiological findings and histology may help in proper management and hence, timely treatment of the patient

Molecular and Genetic Basis of Intellectual Disability in Pakistani Population

Intellectually disability is a genetically heterogeneous disorder that results due to impairment in development of nervous system. Intellectual disability is characterized by an IQ level below 70 and limitation in adaptive behaviors. Prevalence of intellectual disability is estimated 2-3% worldwide. In Pakistani population, prevalence of intellectual disability is higher than the average. Numerous factors contribute to the elevated prevalence. These include poor nutrition, deprived social-economic conditions, birth defects, and consanguinity. Genetic factors contributing to intellectual disability have not been studied comprehensively in Pakistani population. The present project was conducted at the Genetic Diseases Laboratory, Center of Excellence in Molecular Biology (CEMB), Lahore. The aim of study was to uncover genetic determinants of intellectual disability in local population. Thirty two families with multiple intellectually disabled patients are enrolled from various cities. Genetic analysis of these families to determine causative genetic variations, homozygosity mapping and next generation sequencing was performed. The results were further verified by in-silico tools and Sanger sequencing. Two families designated PKMR198 and PKMR 216 showed linkage to MRT23 and MRT9 respectively. Two families, PKMR 205 and PKMR 213, showed novel linkage at chromosome 13 and chromosome 1 respectively. Exome sequencing was utilized to find pathogenic DNA changes that have potential to cause intellectual disability. In three families recurrent mutations were found in reported genes for intellectual ability. PKMR29 showed segregation of recurrent mutation c.881A>G in POMT2. PKMR115 presented mutation c.57G>A in SRD5A3. In PKMR184, recurrent mutation c.5769delT was present in SPG11. Novel pathogenic variations were found in ten genes known to be involved in intellectual disability. These pathogenic variations were homozygous in affected individuals. In five families PKMR85, PKMR99, PKMR119, PKMR193 and PKMR133 novel pathogenic missense variations in MED23_c.506A>G, SYNE1_c.939G>C, PGAP1_c.2276A>G, ARL13B_c.599G>A and DOCK8_c.295G>A were segregated with intellectual disability respectively. In another three families PKMR79, PKMR212 and PKMR224 novel disease causing frameshifts variants AP4M1_c.1287delG, ZFYVE26_c.1630_1631delTC and MKKS_c.775delA showed segregation with intellectual disability respectively. One family PKMR102 segregates stop gain variation ASPM_c.3977G>A with microcephaly. A canonical splice site variation AP4S1_c.139-2A>G at splice acceptor site was found segregating with disease phenotype in family PKMR216. In addition, the results revealed pathogenic genetic variations in nine novel candidate genes. In four families PKMR153 PKMR174, PKMR195 and PKMR213 missense damaging variations GPAA1_c.527G>C, MEGF9_c.686G>A, WFDC1_c.634G>A and TMEM222_c.214G>A were segregated with the neurologic impairment. In four families PKMR64, PKMR200, PKMR206 and PKMR215 novel truncating disease causing variations CAPN12_c.658_659delAA, UBE2J2_c.77_78delAA, CCDC82_c.373delG and PUS7_c.89_90delCA showed segregation respectively. In PKMR72 a silent and splice site variation of MDGA2 (c.2232A>G) is segregating. All known and novel pathogenic variations were homozygous in intellectually disable patients and segregate with autosomal recessive inheritance. These findings further expand the existing repertoire of genes involved in ARID.