Hypercholesterolemia is a strong determinant of mortality and morbidity associated with cardiovascular diseases and a major contributor to the global disease burden. Mutations in four genes (LDLR, APOB, PCSK9 and LDLRAP1) account for the majority of cases with familial hypercholesterolemia. However, a substantial proportion of adults with hypercholesterolemia do not have a mutation in any of these four genes. This indicates the probability of having other genes with a causative or contributory role in the pathogenesis of hypercholesterolemia and suggests a polygenic inheritance of this condition. Here in, we review the recent evidence of association of the genetic variants with hypercholesterolemia and the three lipid traits; total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C), their biological pathways and the associated pathogenetic mechanisms. Nearly 80 genes involved in lipid metabolism (encoding structural components of lipoproteins, lipoprotein receptors and related proteins, enzymes, lipid transporters, lipid transfer proteins, and activators or inhibitors of protein function and gene transcription) with single nucleotide variants (SNVs) that are recognized to be associated with hypercholesterolemia and serum lipid traits in genome-wide association studies and candidate gene studies were identified. In addition, genome-wide association studies in different populations have identified SNVs associated with TC, HDL-C and LDL-C in nearly 120 genes within or in the vicinity of the genes that are not known to be involved in lipid metabolism. Over 90% of the SNVs in both these groups are located outside the coding regions of the genes. These findings indicates that there might be a considerable number of unrecognized processes and mechanisms of lipid homeostasis, which when disrupted, would lead to hypercholesterolemia. Knowledge of these molecular pathways will enable the discovery of novel treatment and preventive methods as well as identify the biochemical and molecular markers for the risk prediction and early detection of this common, yet potentially debilitating condition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0488-4) contains supplementary material, which is available to authorized users.

Hemoglobinopathies are the most common single-gene disorders in the world. Their prevalence is predicted to increase in the future, and low-income hemoglobinopathy-endemic regions need to manage most of the world's affected persons. International organizations, governments, and other stakeholders have initiated national or regional prevention programs in both endemic and nonendemic countries by performing population screening for α- and β-thalassemia, HbE disease, and sickle cell disease in neonates, adolescents, reproductive-age adults (preconceptionally or in the early antenatal period), and family members of diagnosed cases. The main aim of screening is to reduce the number of affected births and, in the case of sickle cell disease, reduce childhood morbidity and mortality. Screening strategies vary depending on the population group, but a few common screening test methods are universally used. We discuss the salient features of population-screening programs around the globe as well as current and proposed screening test methodologies.

Human cutaneous leishmaniasis (CL) caused by Leishmania donovani, a pathogen more usually associated with visceral leishmaniasis, is now endemic in Sri Lanka. This report details the characteristics of 200 patients with locally acquired CL, who were recruited prospectively for an ongoing study into the genetic susceptibility to CL in Sri Lanka. In each case, the CL was confirmed by the demonstration of amastigotes in a direct smear and/or promastigotes in a culture. Although only 82% of the Sri Lankan population is Sinhalese, all 200 patients belonged to this ethnic group. The patients had a median age of 32 years (range=4-80 years). Most of them each had a single, non-tender, non-itching and dry lesion which had started as a papule and then gradually enlarged and ulcerated, with changes in the surrounding skin. None of the patients had any signs of systemic disease. Eleven (5.5%) each had at least one other affected family member. Patients with multiple lesions were most likely to be found in families with more than one affected member (P=0.002) but multiple lesions were not associated with diabetes mellitus (P>0.05). Although the results of passive detection under-estimate the true occurrence of a disease, the present data point towards enhanced susceptibility to CL among the Sinhalese and/or certain individuals, possibly determined by genetic factors.

BackgroundCenani-Lenz Syndactyly (CLS) syndrome is a rare autosomal recessive disorder characterized by syndactyly and oligodactyly of fingers and toes, disorganization and fusion of metacarpals, metatarsals and phalanges, radioulnar synostosis and mesomelic shortness of the limbs, with lower limbs usually being much less affected than upper limbs.Case presentationwe report here two patients, born to consanguineous Sri Lankan parents, present with bilateral postaxial oligodactyly limited to upper limbs. While the proband has no noticeable facial dysmorphism, renal impairments or cognitive impairments, his affected sister displays a few mild facial dysmorphic features. Whole exome sequencing of the proband showed a novel deleterious homozygous mutation (c.1348A > G) in the LRP4 gene, resulting in an Ile450-to-Val (I450V) substitution.ConclusionThis recessive mutation in LRP4 confirmed the diagnosis of CLS syndrome in two patients present with isolated hand syndactyly. This is the first reported case of CLS syndrome in a family of Sri Lankan origin.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0646-1) contains supplementary material, which is available to authorized users.

Nearly all twin registers are based in developed countries and there is no twin register in the devel opi ng w or l d. Our objecti ves w er e to i ni ti ate the pr ocess of establ i shi ng a nati onw i de tw i n register in Sri Lanka by starting a volunteer register first and working towards a population-based r egi ster. Regul ar new spaper adver ti sements, featur e ar ti cl es, r adi o tal k s, and tel evi si on pr ogr ammes w er e used to publ i ci se a competi ti on for tw i ns, thei r par ents/r el ati ves and fr i ends r equesti ng them to par ti ci pate by sendi ng i n detai l s of tw i ns. The competi ti on r an fr om 28 M ar ch 1997 for a per i od of 3 months. I t offer ed pr i zes for thr ee w i nner s sel ected by dr aw i ng l ots. A dver ti sements hi ghl i ghted the objecti ve of the competi ti on as establ i shi ng a tw i n r egi ster for futur e r esear ch and emphasi sed that i nfor med consent w oul d be obtai ned for i ndi vi dual r esear ch pr ojects. Those w ho r egi ster ed compr i se 4602 tw i n pai r s (same sex: mal e-1564, femal e-1885; di ffer ent sex-1153), 80 sets of tr i pl ets (same sex: mal e-17, femal e-31; di ffer ent sex-42) and tw o sets of quadr upl ets (di ffer ent sex). The ol dest tw i ns, tr i pl ets, quadr upl ets ar e 85, 46, and 5 year s ol d, r especti vel y; 88.0% of tw i ns ar e l ess than 30 year s ol d. A l though other s have pr evi ousl y used media publicity to enrol twins in twin registers, we believe this to be the first time that twins have been enr ol l ed thr ough competi ti on. We have mor e young tw i ns, and our gender and zygosi ty pr opor ti ons after appl yi ng Wei nbur g's r ul e do not match the pr opor ti ons expected fr om a vol unteer tw i n sampl e. Establ i shi ng a tw i n r egi ster for r esear ch pur poses has pr oved possi bl e i n a devel opi ng countr y. Twin Research (2000) 3, 202-204. Keyw or ds: vol unteer regi ster, competi ti on for tw i ns, new spaper adverti sements, Wei nberg di fferenti al method