Potential oligogenic disease of mental retardation, short stature, spastic paraparesis and osteopetrosis

Abdulaziz Alsemari,1 Mohanned Alsuhaibani,2 Rawabi Alhathlool,1 Bayan Mamdouh Ali1 1Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; 2Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Abstract: The interaction of multiple genetic factors, as opposed to monogenic inheritance, has been suspected to play a role in many diseases. This interaction has been described as an oligogenic inheritance model, which may be a useful tool in explaining certain clinical observations. The purpose of this study was to search for novel genetic defects among members of a family with traits that include mental retardation, short stature, osteopetrosis, calcification of basal ganglia, and thinning of the corpus callosum. In the index case (111-4), we identified four homozygous mutations: chromosome 8, intron2 (c.232+1G>A) at CA2 gene; chromosome 15, exon 32 (c.6100C>T) at the SPG11; chromosome 5, exon 11 (c.1015G>A) at the MCCC2; and chromosome 9, exon 9 (C.1193g>t) at the LARP gene. The mutations were confirmed by Sanger sequencing, and both parents were observed to be heterozygous for the four mutations. A moderately affected sister of the index case was homozygous for only three mutations in CA2, LARP, and Mccc2, while a nonaffected sister was heterozygous for three mutations in CA2, LARP, and MCCC2 and negative for SPG11. The clinical features of the two affected sisters can be explained distinctively by each homozygous mutation in an oligogenic pattern of inheritance. This family represents an example of an oligogenic pattern of inheritance of mental retardation, short stature, spastic paraparesis, and osteopetrosis. Keywords: mental retardation, short stature, spastic paraparesis, CA2, SPG11, LARP, oligogeni

Public Awareness on Cord Blood Banking in Saudi Arabia

Background. In the last decade, cord blood (CB) has proven to be a valuable source of hematopoietic stem cells for transplantation to treat many hematological disorders. Since then, many CB banks have been established worldwide. Our aim was to estimate the level of public awareness of CB banking in Saudi Arabia. Study Design and Methods. A self-administered questionnaire of 22 multiple choices was conveniently distributed, consisting of demographics, awareness measure, attitude toward banking preference, and donation for research data. Results. A total of 1146 participants have completed the questionnaire. The majority were young female 19–25 years old (26%), who are college graduates (57%) with middle class socioeconomic status (82%). The subjective assessment of the overall knowledge was inadequate (66%). For the objective assessment, 12 questions were asked about CB source, collection, storage, and usage. Only half of the subjects (52%) knew that CB is a source of stem cells. More than half did not know the main use of CB. About half did not know about the method of collection nor the condition of storing. Conclusion. This study shows a high lack of knowledge about CB banking. More than half of the subjects were unaware of CB banking and its uses. However, most subjects are accepting CB storage, which anticipates great impact and efficacy on educational programs. Moreover, the data demonstrated that health professionals were not the source of knowledge. We recommend having comprehensive educational campaigns with clear information about CB banking to facilitate positive perspectives towards donation and scientific research

Expression of Programmed Cell Death-L1 (PD-L1) Protein and Mismatch Repair Mutations in Orbital Tumours-a Pilot Study

Purpose: Programmed cell death protein 1 (PD-1) and DNA mismatch repair (MMR) deficiency play an important role in tumour progression and response to treatment. Both markers have been studied in some ocular tumours but little is known about these markers in orbital tumours. This pilot study reports on PD-L1 expression and MMR mutations using next generation sequencing (NGS) in specific orbital tumours. Methods: We reviewed surgical specimens from patients with rhabdomyosarcoma, adenoid cystic carcinoma (ACC), pleomorphic adenoma (PA) and biopsy negative tissue from orbital tumours used as a control. immunohistochemistry (IHC) was performed on Formalin fixed paraffin embedded tissue using a PD-L1 antibody. DNA was extracted for targeted gene panel NGS of the MMR genes PMS2, MLH1, MSH6 and MSH2. Results: The study included 17 orbital specimens. Scattered membrane PD-L1 staining was noted in 3/6 rhabdomyosarcoma specimens without an accompanying lymphocytic infiltrate. PD-L1 immunostaining was absent in 3/3 ACC, and 5/6 PA specimens. PD-L1 immunostaining was not detected in 2/2 control specimens. 4/17 samples shared the same pathogenic mutation in the MLH1 gene, including 3/6 rhabdomyosarcoma and 1/3 ACC samples. 1/6 PA samples had a mutation in MSH6. Conclusions: Our study demonstrated scattered, non-quantifiable or absent PD-L1 staining in a limited sample of orbital tumours suggesting that PD-1/PD-L1 inhibitor therapy may not be useful in treatment of malignant orbital tumours (rhabdomyosarcoma and ACC) when refractory to conventional therapy. Our pilot study suggest that PD-L1/MMR axis might not play a major role in the pathogenesis of primary orbital tumour

Conjunctival Pediatric Follicular Lymphoma: Case Report and Literature Review

Follicular lymphoma (FL) is the second most commonly reported B-cell lymphoma and accounts for 6% of all orbital lymphomas. FL presentation in the pediatric population is rare. This study reported an 18-year-old male with a pink elevated lesion in the conjunctiva of the left eye and normal ocular parameters. Following a complete excisional biopsy, the lesion was oval and smooth grossly and showed dense proliferation with a high nuclear-cytoplasmic ratio microscopically. Immunohistochemical studies revealed positive CD20 and bcl-6 while bcl-2 was negative, which is a common feature for pediatric FL in contrast to bcl-2 positivity found by immunohistochemistry in FL occurring in adult patient population. No signs of recurrence were observed over 2 years of follow-up. This study adds a new case to the existing few reports. Interestingly, all reported cases were males including the patient, mean duration of onset was 5 months, and mean duration of follow-up was 18.4 months. The authors emphasize that total surgical excision with close monitoring is reasonable management of such clinical entity

Correction to: Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism

Correction After publication of the article [1], it has been brought to our attention that there is a nomenclature issue with this article. At the time of acceptance, the VARS2 mutation was considered equivalent to the VARS2 mutation. However, this has changed so that VARS now only refers to shorter mitochondrial sequence of valyl-tRNA synthesase containing 1093 amino acids. “Therefore, in the context of this article, every usage of “VARS2” should be replaced with “VARS” when referring to the causative variant”

Prevalence of Fast Food Intake among a Multi-Ethnic Population of Young Men and Its Connection with Sociodemographic Determinants and Obesity

Fast food is commonly consumed by young adults. Eating fast food is connected with the risk of obesity and other related diseases. The present study examines the prevalence of fast food intake in a diverse sample of young men. This cross-sectional study included 3600 young men (20–35 years) who resided in Riyadh, KSA. The frequency of fast food intake was assessed using a valid and reliable questionnaire. Weekly and daily intake of fast food were the two outcome variables adopted to assess the intake frequency. Weight and height were measured. Fast food was eaten by 88.8% and 50.1% of participants weekly and daily, respectively. Fast food intake was predicted by the nationality of participants. The highest prevalence of weekly fast food intake (99.7%) was observed among Saudi, Egyptian, and Indian participants, while the lowest rate was observed among Sudanese participants (48.6%). The highest and lowest rates of daily intake were seen among Filipino (83.4%) and Bangladeshi (6.3%) participants. Obesity was another predictor of fast food intake. Obese participants had a significantly higher odds ratio of weekly (OR = 2.89, p = 0.006) and daily (OR = 1.39, p = 0.021) fast food intake than non-overweight/non-obese participants. In conclusion, fast food is frequently consumed by young men in KSA. Our findings link the likelihood of fast food intake to sociodemographic determinants and obesity