Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Rubella-associated hemophagocytic syndrome in an infant

Hemophagocytic syndrome (HPS) is a fulminant disorder characterized pathologically by multiple-organ infiltration of hemophagocytic histiocytes in the lymphoreticular tissues. The characteristic pathologic feature is reactive histiocytic hyperplasia with leukoerythrophagocytosis in a variety of organs. This disorder occurs most often in patients in whom the immune system is compromised and has been associated with a variety of infectious agents, including viruses, bacteria, mycobacteria, spirochetes, fungi, and parasites. The authors describe a 2.5-month-old girl with rubella-associated HPS, demonstrated by postmortem liver necropsy

Neonatal hepatitis in 2 siblings with Seckel syndrome

Seckel syndrome was described as the prototype of the primordial bird-head type of dwarfism. We report 2 cases of Seckel syndrome in siblings. Both cases showed peculiar phenotypic features. Autopsy was performed and microscopic examination of the livers displayed histologic features of neonatal hepatitis. Tn addition, our younger patient had central nervous system anomalies such as agenesis of corpus callosum, cerebral cyst, and primitive convolutional pattern. No previous reports of liver disease exist in patients with Seckel syndrome. The pathologic findings of such an unusual association and a review of literature are presented

Joubert syndrome: review and report of seven new cases

Joubert syndrome (JS) is an autosomal-recessive disorder, characterized by hypotonia, ataxia, global developmental delay and molar tooth sign on magnetic resonance imaging. A variety of other abnormalities have been described in children with JS, including abnormal breathing, abnormal eye movements, a characteristic facial appearance, delayed language, hypersensitivity to noise, autism, ocular and oculomotor abnormalities, meningoencephaloceles, microcephaly, low-set ears, polydactyly, retinal dysplasia, kidney abnormalities (renal cysts), soft tissue tumor of the tongue, liver disease and duodenal atresia. Even within siblings the phenotype may vary, making it difficult to establish the exact clinical diagnostic boundaries of JS. We review the clinical characteristics of seven cases that fulfill the criteria of JS

Pheochromocytoma presenting with polydipsia and polyuria in a child

Pheochromocytomas are rare tumors in childhood and can mimic many unrelated diseases due to their various presenting symptoms. While hypertension is the most prevalent finding of pheochromocytomas, polyuria and polydipsia are rare and interesting symptoms. In this study we presented a child with unilateral pheochromocytoma, whose first symptoms were polyuria-polydipsia, and hypertension, which were important clues for pheochromocytoma. With the help of clinical and laboratory findings, patient was diagnosed as pheochromocytoma and referred to surgery; with the removal of the tumor the symptoms disappeared. When the family members were screened for multiple endocrine neoplasia (MEN) syndromes, a bilateral pheochromocytoma was diagnosed in his sister and she was also operated on immediately. In this article we emphasized that polyuria-polydipsia may be the first symptoms of pheochromocytoma in children, the importance of blood pressure measurement in initial physical examination and the familial pattern of pheochromocytoma

The Relationship between Abdominal Aortic Intima-Media Thickness and Lipid Profile in Neonates Born to Mothers with Preeclampsia

Neonates born to mothers with preeclampsia are known to be associated with lipid alterations that might increase the risk for cardiovascular disease in adult life. The aim of this study was to investigate the effect of preeclampsia on lipid metabolism, aortic intima-media thickness (aIMT) and subsequent atherogenic risk in newborn infants. Aortic intima-media thickness was measured in 60 neonates of mothers with preeclampsia (group I; 30 neonates of mothers with preeclampsia and group II; 30 neonates of mothers with severe preeclampsia) and 30 healthy neonates (group III). Maternal and cord serum lipid profiles were determined in all groups. Mean abdominal aIMT measurements were higher in the neonates born to mothers with preeclampsia (group I; 0,36 +/- 0,03 mm and group II; 0,36 +/- 0,04 mm) compared with the control group (group III; 0,33 +/- 0,03 mm, p=0,006). Serum triglyceride levels were significantly higher in the neonates born to mothers with preeclampsia (group I; 39,2 +/- 42,0 mg/dl and group II; 39,5 +/- 56,5 mg/dl) compared with the control group (group III; 14,9 +/- 18,8 mg/dl, p = 0,039). Serum HDL cholesterol levels were significantly lower in the neonates born to mothers with precclampsia (group I; 17,3 +/- 12,3 mg/dl and group II; 17,1 +/- 12,8 mg/dl) compared with the control group (group III; 27,6 +/- 13,0 mg/dl, p = 0,002). In conclusion; neonates of mothers with preeclampsia have significantly higher aIMT with lipid alterations. This may play a role in the pathogenesis of atherosclerosis in adult life.Neonates born to mothers with preeclampsia are known to be associated with lipid alterations that might increase the risk for cardiovascular disease in adult life. The aim of this study was to investigate the effect of preeclampsia on lipid metabolism, aortic intimamedia thickness (aIMT) and subsequent atherogenic risk in newborn infants. Aortic intima-media thickness was measured in 60 neonates of mothers with preeclampsia (group I; 30 neonates of mothers with preeclampsia and group II; 30 neonates of mothers with severe preeclampsia) and 30 healthy neonates (group III). Maternal and cord serum lipid profiles were determined in all groups. Mean abdominal aIMT measurements were higher in the neonates born to mothers with preeclampsia (group I; 0.36 +/- 0.03 mm and group II; 0.36 +/- 0.04 mm) compared with the control group (group III; 0.33 +/- 0.03 mm, p = 0.006). Serum triglyceride levels were significantly higher in the neonates born to mothers with preeclampsia (group I; 39.2 +/- 42.0 mg/dl and group II; 39.5 +/- 56.5 mg/dl) compared with the control group (group III; 14.9 +/- 18.8 mg/dl, p = 0,039). Serum HDL cholesterol levels were significantly lower in the neonates born to mothers with preeclampsia (group I; 17.3 +/- 12.3 mg/dl and group II; 17.1 +/- 12.8 mg/dl) compared with the control group (group III; 27.6 +/- 13.0 mg/dl, p = 0.002). In conclusion; neonates of mothers with preeclampsia have significantly higher aIMT with lipid alterations. This may play a role in the pathogenesis of atherosclerosis in adult life.</p

Serum leptin levels in patients with childhood immune thrombocytopenic purpura

Acute immune thrombocytopenic purpura (ITP) induces thrombocytopenia by means of an autoimmune mechanism. Recent studies suggested that T helper immune response is responsible for the pathogenesis of chronic ITP. Despite several studies that were carried out, we do not have a clue as to what triggers the autoimmunity. Leptin is a 16-kd protein secreted from the adipose tissue. Leptin is structurally similar to interleukin (IL)-2, IL-6, and IL-15. The structural similarities between leptin receptor and hernatopoietic cytokine receptors suggested that leptin could play a role in hematopoiesis and immune function. Recent studies suggested that leptin could play an important role in autoimmunity. We made a prospective analysis of a series of 39 newly diagnosed acute childhood ITP in a year period. Serum leptin levels were obtained after diagnosis and before treatment and all patients were followed up at least 6 months to designate acute or chronic event. We conclude that in childhood acute ITP, leptin did not play a role in the pathophysiology of the disease. Further investigations are needed to examine what triggers T cells and how the autoimmune disease became

Prenatal ultrasonographic diagnosis of rhizomelic chondrodysplasia punctata by detection of rhizomelic shortening and bilateral cataracts

Antenatal sonographic diagnosis of rhizomelic chondrodysplasia punctata depends on recognization of the combination of rhizomelic bone shortening and epiphyseal stippling. This is the only report of prenatal ultrasonographic diagnosis of bilateral cataracts in a fetus with rhizomelic chondrodysplasia punctata (type 1). Also, this is the first report of severe rhizomelic limb shortening, and bilateral cataracts prior to the recognization of epiphyseal stippling. Copyright (C) 2005 S. Karger AG, Basel

Nonketotic hyperosmolar coma associated with splenic rupture in congenital afibrinogenemia

Nonketotic hyperosmolar coma is uncommon in children. Splenic rupture in congenital afibrinogenemia is also a rare event. The authors described a 5-year-old girl with congenital afibrinogenemia who presented with nonketotic hyperosmolar coma associated with spontaneous splenic rupture. Management consisted of correction of the nonketotic hyperosmolar condition and increasing fibrinogen concentration by blood products, followed by splenectomy, resulting in the survival of the patient