Analysis of the association of NPHS2 and ACTN4 genes polymorphism with nephrotic syndrome in Egyptian children.

BACKGROUND: One of the most common kidney illnesses in developing countries is pediatric nephrotic syndrome (PNS), which is frequently associated with dyslipidemia and edema. The rapid discovery of genes related to NS has aided in the understanding of the molecular mechanics of glomerular filtration. The goal of this study is to determine the relationship between NPHS2 and ACTN4 in PNS youngsters. METHODS: A study with 100 NS children and 100 healthy matched volunteers was conducted. Genomic DNA was extracted from peripheral blood. Single-nucleotide polymorphisms were genotyped using ARMS-PCR. RESULTS: A substantial decline in the level of albumin was found in NS cases (P < 0.001) Further on, a significantly difference in T.C and TG level between healthy and NS patient. Molecular study showed a highly significant difference of NS patients from controls regarding NPHS2 rs3829795 polymorphic genotypes as the GA heterozygous genotype shows highly significant difference from controls (P < 0.001) as well as GA + AA genotypes (P < 0.001) in comparison with GG genotype. Regarding rs2274625, The GA heterozygous genotype showed no statistically significant difference between genotypes and alleles with NS (P = 0.246). Association of AG haplotype NPHS2 rs3829795-rs2274625 haplotypes found a significant association with the risk of developing NS (P = 0.008). Concerning the ACTN4 rs121908415 SNP, there was no link between this mutation and NS children. CONCLUSION: The correlation of AG haplotype NPHS2 rs3829795-rs2274625 haplotypes identified a strong association with the likelihood of getting NS, according to our findings. There was no connection found between the ACTN4 rs121908415 SNP and NS children.

Recurrence pattern of non-syndromic familial congenital heart diseases among a large cohort of families from Egypt.

BACKGROUND: Congenital heart diseases (CHD) are the commonest congenital anomalies with increased risk in children born from families with affected members. However, various recurrence patterns of CHDs have been reported in different populations. Therefore, this work aimed to assess the recurrence patterns of CHDs in a large sample of Egyptian families. METHODS: From January 2020 to October 2021, non-syndromic children with confirmed CHDs were recruited. Data were collected from guardians of the recruited children and hospital records, including the index case's cardiac diagnosis and CHD diagnosis of other affected family members with to determine their recurrence pattern, consanguinity, and multi-gestation status. RESULTS: A total of 130 recurrent cases with CHD were documented in 1960 families of children with CHD, including 66,989 members. Most recurrences were detected among first-degree relatives 50/130 (38.46%), especially siblings. Discordant recurrence was the most detected pattern (45.38%), followed by concordant recurrence (42.31%), and the least was group concordance. Recurrence rate was the highest for septal defects with left ventricular outflow tract obstruction (LVOTO) (11.8%) and anomalous venous drainage (11.1%), followed by septal defect with right ventricular outflow tract obstruction (RVOTO) (9.4%), isolated ventricular septal defect (VSD) category (8.2%) and LVOTO (8%). Familial recurrence was significant in consanguineous marriages [p = 0.0001; OR (95%CI) = 4.5 (2.25-9.01)] and in multi-gestations siblings: [p = 0.036; OR (95%CI) = 12.5(1.03-6.04)]. CONCLUSION: The recurrence of non-syndromic CHD is evident among first-degree relatives in Egyptian families, with mostly a discordant recurrence pattern. Recurrence was more notable in septal defects with LVOTO, anomalous venous drainage, septal defect with RVOTO, isolated VSD, and isolated LVOTO diagnostic categories. This finding will significantly impact family counseling, emphasizing higher recurrence in consanguineous parents.

Screening for the Most Common Mutations of CFTR Gene among Egyptian Children with Difficult-to-Treat Asthma.

Cystic fibrosis (CF) is panethnic autosomal recessive disease that affects the exocrine glands of pancreas, lungs, and intestine. It is often misdiagnosed in developing countries as difficult-to-treat asthma. We enrolled 150 Egyptian families with one or more probands who were complaining of difficult-to-treat asthma, and 112 cases were studied extensively through history taking including pedigree construction and clinical examination. In addition, spirometry and computed tomography of the chest were done in selected cases. All cases were subjected to quantitative sweat chloride test and molecular screening for the three most common mutations of cystic fibrosis transconductance regulator ( CFTR ) gene ( ΔF508 , G542X , W1282X ) using amplification refractory mutation system (ARMS) technique. Probands of difficult-to-treat asthma comprised 66 males and 46 females; their age range was 1 to 14 years. Sixty-one probands (54.5%) were carriers of one or more of the studied mutations (36 cases and 25 carriers). Six carriers of single mutations had mild respiratory symptoms and negative sweat test. The most common allele was ΔF508 , 60 alleles in 56 individuals (4 were homozygous ΔF508 / ΔF508 ) followed by W1282X in 25 individuals and G542X in 12 individuals. Allele W1282X had an increased risk of recurrent chest infection and bronchiectasis. Moreover, cases with two mutations had more severe symptoms compared with those with a single mutation. CFTR mutations and CF-related syndromes are not rare as thought in Egypt, especially among the high-risk difficult-to-treat asthma. The readily available ARMS technique is recommended for ΔF508 and/or W1282X screening on priority basis among these children.

A novel fibrillin-1 mutation in an egyptian marfan family: A proband showing nephrotic syndrome due to focal segmental glomerulosclerosis.

Marfan syndrome (MFS), the founding member of connective tissue disorder, is an autosomal dominant disease; it is caused by a deficiency of the microfibrillar protein fibrillin-1 (FBN1) and characterized by involvement of three main systems; skeletal, ocular, and cardiovascular. More than one thousand mutations in FBN1 gene on chromosome 15 were found to cause MFS. Nephrotic syndrome (NS) had been described in very few patients with MFS being attributed to membranoproliferative glomerulonephritis secondary to infective endocarditis. Focal segmental glomerulosclerosis (FSGS) had been reported in NS in conjunction with MFS without confirming the diagnosis by mutational analysis of FBN1. We hereby present an Egyptian family with MFS documented at the molecular level; it showed a male proband with NS secondary to FSGS, unfortunately, we failed to make any causal link between FBN dysfunction and FSGS. In this context, we review the spectrum of renal involvements occurring in MFS patients.

Novel homozygous SLC29A3 mutations among two unrelated Egyptian families with spectral features of H-syndrome.

OBJECTIVES: H syndrome and pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID) had been described as two autosomal recessive disorders. We aim to screen for pathogenic SLC29A3 mutations in two unrelated Egyptian families with affected siblings of these overlapping syndromes. METHODS: Clinical, laboratory, histopathological, and radiological characteristics of individuals probably diagnosed as H and/or PHID syndrome were reported. Mutation analysis of SLC29A3 gene was performed for all members of the two Egyptian families. RESULTS: All affected individuals were females; proband of family-I (A1961) displayed overlapping features of H syndrome and PHID, while her younger brother (A1962) was asymptomatic. A1961 presented with previously undescribed features; absent pectoralis major muscle and a supracondylar bony spur in left humerus. In family-II, probands (A1965 and A1966) had clinical features consistent with classical H syndrome with unique early onset of cutaneous phenomena at birth. Mutation analysis of SLC29A3 revealed homozygous mutation previously reported in literature c.1279G>A [p.G427S] in A1961 and unexpectedly in the asymptomatic A1962 of family-I. Probands of family-II were homozygous for a novel mutation c.401G>A [p.R134H], in the same codon that was published in an Indian boy [p.R134C]. CONCLUSIONS: We emphasize the inter- and intra-familial genetic heterogeneity among Egyptian patients with overlapping features of SLC29A3 disorders. This suggests the presence of other factors like regulatory genes or epigenetic factors that may explain variable disease manifestations and severity.

Phenotype-genotype updates from familial Mediterranean fever database registry of Mansoura University Children' Hospital, Mansoura, Egypt.

BACKGROUND: Familial Mediterranean fever (FMF) is autosomal recessive disease that affects people from Mediterranean region, Europe and Japan. Its gene (Mediterranean fever [MEFV]) has more than 100 mostly non-sense mutations. OBJECTIVES: The objective of the following study is to provide some phenotype-genotype correlates in FMF by categorizing the Egyptian FMF cases from Delta governorates after analysis of the four most common mutations of MEFV gene (M680I, M694I, M694V, V726A). SUBJECTS AND METHODS: Clinically, suspected FMF cases using Tel-Hashomer criteria were enrolled in the study. Cases were referred to Mansoura University Children's Hospital that serves most of the most middle Delta governorates, in the period from 2006 to 2011. Subjects included 282 males and 144 females, mean age of onset 9.3 ± 2.2 years. All cases were analyzed for these mutations using amplification refractory mutation system based on the polymerase chain reaction technique. Five FMF patients agreed to undergo renal biopsy to check for development of amyloidosis. Analysis of data was carried out using SPSS (SPSS, Inc., Chicago, IL, USA). RESULTS: Mutation was found in 521 out of 852 studies alleles, the most frequent is M694V (35.4%) followed by M694I, V726A and M680I. 11 cases were homozygous; 7 M694V, 3 M680I and only one M694I case. Severe abdominal pain occurred in 31 (7.28%) but severe arthritis in 103 cases (24.2%). Strong association was found between arthritis and homozygous mutant compared with single and double heterozygous (72.7% vs. 33.3% and 20.24%, P < 0.001). Four amyloid cases were M694V positive. CONCLUSION: M694V allele is the most common among Egyptian FMF especially those with amyloidosis. We recommend routine check for amyloidosis in FMF cases to statistically validate this link.

Disruptive behavior in Down syndrome children: a cross-sectional comparative study.

BACKGROUND AND OBJECTIVES: Down syndrome (DS) is associated with intellectual disability, and patients with DS show significant psychopathology. The objectives of this study were to estimate the prevalence of disruptive behavior in DS patients compared to their siblings, and to find any association between the disruptive behavior and the degree of intelligence. DESIGN AND SETTINGS: This is a cross-sectional comparative study done in Mansoura University Children's Hospital during the period March 1, 2012-February 28, 2013. SUBJECTS AND METHODS: In this study, 100 cases of DS and an equal number of their brothers/sisters were enrolled in the study. The Arabic version of Vineland Adaptive Behavior Scale was used for assessing social and mental intelligence quotient (IQ). The Arabic version of Mini International Neuropsychiatric Interview for Children (MINI-KID) and disruptive behavior disorder (DBD) rating scale were used for assessing disruptive behavior disorders. RESULTS: Both social and mental IQs were significantly higher in non-DS than in DS cases. The prevalence of different variants of attention deficit/hyperactive disorder (ADHD)-impulsive, inattentive, and combined types-was significantly lower in non-DS than in DS cases; however, there was no statistical difference between both groups as regards oppositional defiant disorder and conduct disorder (CD). Also among DS cases, impulsive and combined types varied significantly with the degree of their IQ. CONCLUSION: ADHD was more common among DS patients with a special impact of IQ on the type of psychiatric illness. We recommend psychiatric assessment for DS patients as a part of multidisciplinary management.

Cystinosis as a lysosomal storage disease with multiple mutant alleles: Phenotypic-genotypic correlations.

Cystinosis is an autosomal recessive lysosomal storage disease with an unclear enzymatic defect causing lysosomal cystine accumulation with no corresponding elevation of plasma cystine levels leading to multisystemic dysfunction. The systemic manifestations include a proximal renal tubular defect (Fanconi-like), endocrinal disturbances, eye involvements, with corneal, conjunctival and retinal depositions, and neurological manifestations in the form of brain and muscle dysfunction. Most of the long-term ill effects of cystinosis are observed particularly in patients with long survival as a result of a renal transplant. Its responsible CTNS gene that encodes the lysosomal cystine carrier protein (cystinosin) has been mapped on the short arm of chromosome 17 (Ch17 p13). There are three clinical forms based on the onset of main symptoms: nephropathic infantile form, nephropathic juvenile form and non-nephropathic adult form with predominant ocular manifestations. Avoidance of eye damage from sun exposure, use of cystine chelators (cysteamine) and finally renal transplantation are the main treatment lines. Pre-implantation genetic diagnosis for carrier parents is pivotal in the prevention of recurrence.

Sporadic Fibrodysplasia Ossificans Progressiva in an Egyptian Infant with c.617G > A Mutation in ACVR1 Gene: A Case Report and Review of Literature.

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant severe musculoskeletal disease characterized by extensive new bone formation within soft connective tissues and unique skeletal malformations of the big toes which represent a birth hallmark for the disease. Most of the isolated classic cases of FOP showed heterozygous mutation in the ACVR1 gene on chromosome 2q23 that encodes a bone morphogenetic protein BMP (ALK2). The most common mutation is (c.617G > A) leading to the amino acid substitution of arginine by histidine (p.Arg206His). We currently report on an Egyptian infant with a sporadic classic FOP in whom c.617G > A mutation had been documented. The patient presented with the unique congenital malformation of big toe and radiological evidence of heterotopic ossification in the back muscles. The triggering trauma was related to the infant's head, however; neither neck region nor sites of routine intramuscular vaccination given during the first year showed any ossifications. Characterization of the big toe malformation is detailed to serve as an early diagnostic marker for this rare disabling disease.

Platelet count and serum thrombopoietin level as predictors for morbidity and/or mortality in thrombocytopenic neonates.

BACKGROUND: Serum thrombopoietin in thrombocytopenic infants is largely related to the cause of thrombocytopenia and the underlying disease. Many perinatal factors can affect thrombopoietin level. PATIENTS AND METHODS: A prospective cross-sectional study on 119 thrombocytopenic neonates: 54 full term and 65 preterm had been conducted. Thrombopoietin assay was done using a qualitative enzyme-linked immunosorbent assay technique. The test was repeated on the change of clinical status (recovery or deterioration). RESULTS: Lowering of thrombopoietin level was noted on reversal of platelet count to normal (P<0.001). Survival is significantly related to platelet count in full term (P = 0.04), but insignificant among thrombocytopenic preterms. Platelet count is negatively correlated to thrombopoietin level in neonates both in full term and preterm (r = -0.59, -0.69, respectively, P<0.001). Platelet count was found to be the best predictor for duration of recovery of thrombocytopenia in neonates compared with other factors including thrombopoietin level. CONCLUSION: Thrombocytopenic neonates had high levels of thrombopoietin. Despite the high thrombopoietin level in neonates died with severe thrombocytopenia, yet, mortality is related to the cause and outcome of thrombocytopenia rather than the serum thrombopoietin level. It is recommended to diagnose and treat the underlying cause of thrombocytopenia rather than to generalize the therapy based on thrombopoietin level.

A novel homozygous p.Arg527Leu LMNA mutation in two unrelated Egyptian families causes overlapping mandibuloacral dysplasia and progeria syndrome.

Mandibuloacral dysplasia (MAD) is a rare disease resulting from a mutation of LMNA gene encoding lamins A and C. The most common mutation associated with this disease is a homozygous arginine 527 replacement by histidine. Three female patients originating from two unrelated families from Northeast Egypt were examined. Their growth was retarded; they had microcephaly, widened cranial sutures, prominent eyes and cheeks, micrognathia, dental crowding, hypoplastic mandible, acro-osteolysis of distal phalanges, and joint contractures. In addition, they presented some progeroid features, such as pinched nose, premature loss of teeth, loss of hair, scleroderma-like skin atrophy, spine rigidity, and waddling gait. The clinical presentation of the disease varied between the patient originating from Family 1 and patients from Family 2, suggesting that unknown, possibly epigenetic factors, modify the course of the disease. The first symptoms of the disease appeared at the age of 2.5 (a girl from Family 1), 5, and 3 years (girls from Family 2). All patients had the same, novel homozygous c.1580G>T LMNA mutation, resulting in the replacement of arginine 527 by leucine. Computational predictions of such substitution effects suggested that it might alter protein stability and increase the tendency for protein aggregation, and as a result, might influence its interaction with other proteins. In addition, restriction fragment-length polymorphism analysis performed in 178 unrelated individuals showed that up to 1.12% of inhabitants of Northeast Egypt might be heterozygous carriers of this mutation, suggesting the presence of a founder effect in this area.

Mutation analysis of the GLUT2 gene in three unrelated Egyptian families with Fanconi-Bickel syndrome: revisited gene atlas for renumbering.

BACKGROUND: Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder caused by defects in the facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene which codes for the glucose transporter protein 2 expressed in hepatocytes and renal tubular cells causing a defect in carbohydrate metabolism, hepatomegaly, severe hypophosphatemic rickets and failure to thrive. SUBJECTS AND METHODS: Among 17 unrelated Egyptian families with heritable renal tubular acidosis, three families clinically suspected as FBS were enrolled for this study after providing written informed consent. The three families had positive consanguinity and index cases with characteristic clinical features of FBS (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy). Laboratory work-up included urinalysis, renal and liver function tests, fasting and postprandial blood sugar, serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile and arterial blood gas analysis. Imaging studies included bone survey and abdominal ultrasound. Liver biopsy was performed to confirm pathological diagnosis of the liver enlargement. Molecular analysis was performed for all family members-polymerase chain reaction followed by direct sequencing of the coding segments as well as the flanking introns. RESULTS: Three different mutations were detected, one specific for each family, including two new mutations. In the first family, exon 3, two bases (GA) were deleted (c.253_254delGA causing a frameshift mutation (p. Glu85fs); the patient presented with early symptoms but unfortunately died despite adequate treatment. In the second family, a mutation was found in exon 6, in the splicing acceptor site with intron 5 (c.776-1G>C or IVS5-1G>A). The third family showed a missense mutation C-to-T substitution at c.1250 (c.1250C>T) causing change of codon 417 (CCG) for proline to CTG for leucine (p. P417L); this is a well-known mutation in the Arab population previously localized in exon 9; however, it is currently renumbered to exon 10. CONCLUSION: Neither the new mutations nor the reported one were particularly more frequent; however, the third mutation (c.1250C>T) needs more attention in survey studies especially if performed in Arab patients as it has been renumbered because of the 'change' of gene structure since the initial reports.

Fanconi-Bickel syndrome as an example of marked allelic heterogeneity.

Renal tubular acidosis (RTA) encompasses many renal tubular disorders characterized by hyperchloremic metabolic acidosis with a normal anion gap. Untreated patients usually complain of growth failure, osteoporosis, rickets, nephrolithiasis and eventually renal insufficiency. Fanconi-Bickel syndrome (FBS) is an example of proximal RTA due to a single gene disorder; it is caused by defects in the facilitative glucose transporter 2 gene that codes for the glucose transporter protein 2 expressed in hepatocytes, pancreatic ß-cells, enterocytes and renal tubular cells. It is a rare inherited disorder of carbohydrate metabolism manifested by huge hepatomegaly [hence it is classified as glycogen storage disease (GSD) type XI; GSD XI], severe hypophosphatemic rickets and failure to thrive due to proximal renal tubular dysfunction leading to glucosuria, phosphaturia, generalized aminoaciduria, bicarbonate wasting and hypophosphatemia. The disorder has been reported from all parts of Europe, Turkey, Israel, Arabian countries, Japan and North America. Many mutant alleles have been described, its exact frequency is unknown and there is no single mutation found more frequently than the others. The presence of consanguinity in affected families suggests an autosomal recessive pattern of inheritance. New cases of FBS have been recently reported in the Middle and Far East in collaboration with specialized centers. Two novel mutations have been discovered in two unrelated Egyptian families. The first was two bases deletion, guanine and adenine, (c.253_254delGA) causing a frameshift mutation (p. Glu85fs) and the second is mutation in exon6 in splicing acceptor site with intron5 (c.776-1G>C or IVS5-1G>A). Moreover, a new different mutation was described in a 3 year old Indian boy.

p.R672C mutation of MYH3 gene in an Egyptian infant presented with Freeman-Sheldon syndrome.

OBJECTIVE: To define the mutation type in a clinically suspected Egyptian child with Freeman-Sheldon syndrome (FSS); it involves certain skeletal malformations with some facial characteristics; skeletal malformations include camptodactyly with ulnar deviation, talipes equinovarus, while the facial characteristics include deep-sunken eyes with hypertelorism, long philtrum, small pinched nose and pursed mouth. METHODS: Amplification of exon 17 of the embryonic myosin heavy chain (MYH3) gene was done using one forward and two different reverse primers, and then the cleaned PCR product was sequenced. RESULT: A de novo missense mutation (c.2014C>T with replacement C > Y) in MYH3 gene leading to change of arginine at position 672 by cytosine in protein sequence. CONCLUSION: Mutation analysis remains to be the standard way for definitive diagnosis in FSS. The authors currently report, for the first time in an Egyptian infant aged 16 months who presented with FSS, a c.2014C>T missense mutation of MYH3 gene, with no family history or consanguinity.

Fanconi Bickel Syndrome: Novel Mutations in GLUT 2 Gene Causing a Distinguished Form of Renal Tubular Acidosis in Two Unrelated Egyptian Families.

Background. Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder caused by defects in facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene mapped on chromosome 3q26.1-26.3, that codes for the glucose transporter protein 2. Methods. Two unrelated Egyptian families having suspected cases of FBS were enrolled after taking a written informed consent; both had positive consanguinity, and index cases had evidences of proximal renal tubular defects with hepatomegaly; they were subjected to history taking, signs of rickets as well as anthropometric measurements. Laboratory workup included urinalysis, renal and liver function tests including fasting and postprandial blood sugar; serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile, and detailed blood gas. Imaging including bone survey and abdominal ultrasound, and liver biopsy were done to confirm diagnosis. Molecular analysis of the GLUT2 gene was done for DNA samples extracted from peripheral blood leukocyte. All coding sequences, including flanking introns in GLUT2 gene, were amplified using PCR followed by direct sequencing. Results. Two new mutations had been detected, one in each family, in exon 3 two bases (GA) were deleted (c.253 254delGA) and in exon 6 in the second family, G-to-C substitution at position-1 of the splicing acceptor site (c.776-1G>C or IVS5-1G>A). Conclusion. FBS is a rare disease due to mutation in GLUT2 gene; many mutations were reported, about half were novel mutations; yet none of these mutations is more frequent. A more extensive survey for the most frequent mutations among FBS has to be contemplated to allow for use of molecular screening tests like ARMS.

Vitamin e and N-acetylcysteine as antioxidant adjuvant therapy in children with acute lymphoblastic leukemia.

Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC) in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL) during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I) have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II) have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX) antioxidant enzyme, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-alpha), liver enzymes, and bone marrow picture). Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

Endothelin-1 and leptin as markers of intrauterine growth restriction.

OBJECTIVE: To explore the role of endothelin-1 (ET-1) and leptin in intrauterine growth restriction (IUGR) among preeclamptic and non-pre-eclamptic women. METHODS: Forty three patients with a pregnancy complicated by IUGR, 23 cases with severe pre-eclampsia and 20 cases of non-pre-eclamptic were enrolled. Control group comprised 15 cases with uncomplicated pregnancy. Blood samples from umbilical artery and maternal venous blood were collected at the time of delivery for analysis of ET-1 and leptin levels. Mode of delivery, birth weight and Apgar score were also recorded. RESULTS: The mean maternal and fetal ET-1 level was significantly higher in pregnancies complicated by IUGR than in control group. The mean maternal leptin level was significantly higher in pre-eclamptic patients when compared to non-preeclamptic and control groups. Mean fetal leptin level was significantly lower in patients compared to control; however, when fetal leptin corrected to fetal weight, it was insignificantly different in the both groups. E-mail: m. alhaggar@yahoo.co.uk. CONCLUSION: Maternal plasma ET-1 and leptin correlate with the degree of fetal growth restriction originating from deterioration of placental function. Maternal plasma leptin and ET-1 levels may reflect deterioration in fetal growth.