Zoran Gucev

University Children's Hospital, Skopie, Karpoš, Macedonia

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Publications (84)255.02 Total impact

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    ABSTRACT: Background and objectives: Nephrolithiasis is a prevalent condition that affects 10%-15% of adults in their lifetime. It is associated with high morbidity due to colicky pain, the necessity for surgical intervention, and sometimes progression to CKD. In recent years, multiple monogenic causes of nephrolithiasis and nephrocalcinosis have been identified. However, the prevalence of each monogenic gene in a pediatric renal stone cohort has not yet been extensively studied. Design, setting, participants, & measurements: To determine the percentage of cases that can be explained molecularly by mutations in one of 30 known nephrolithiasis/nephrocalcinosis genes, we conducted a high-throughput exon sequencing analysis in an international cohort of 143 individuals <18 years of age, with nephrolithiasis (n=123) or isolated nephrocalcinosis (n=20). Over 7 months, all eligible individuals at three renal stone clinics in the United States and Europe were approached for study participation. Results: We detected likely causative mutations in 14 of 30 analyzed genes, leading to a molecular diagnosis in 16.8% (24 of 143) of affected individuals; 12 of the 27 detected mutations were not previously described as disease causing (44.4%). We observed that in our cohort all individuals with infantile manifestation of nephrolithiasis or nephrocalcinosis had causative mutations in recessive rather than dominant monogenic genes. In individuals who manifested later in life, causative mutations in dominant genes were more frequent. Conclusions: We present the first exclusively pediatric cohort examined for monogenic causes of nephrolithiasis/nephrocalcinosis, and suggest that important therapeutic and preventative measures may result from mutational analysis in individuals with early manifestation of nephrolithiasis or nephrocalcinosis.
    No preview · Article · Jan 2016 · Clinical Journal of the American Society of Nephrology
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    ABSTRACT: The objective of this study was to assess clinical course and outcome of children with congenital anomalies of the kidney and urinary tract (CAKUT) who had an attack of acute poststreptococcal glomerulonephritis (PSGN). Renal status including blood pressure, proteinuria and glomerular filtration rate was retrospectively analyzed in five children with CAKUT and PSGN at the presentation and during the follow up. In the period 2004-2013, 678 patients were diagnosed and recruited in our CAKUT cohort. During this period, 188 patients were hospitalized with the diagnosis of PSGN. A total of five patients had CAKUT and an episode of PSGN (2.6%). Analysis of the follow-up data revealed that three children fully recovered (bilateral vesicoureteral reflux n = 1, ectopic/hypodysplastic kidney n = 1, ureteropelvic junction obstruction n = 1). One child with bilateral hypodysplasia had progressive worsening of the renal function and has been prepared for renal replacement therapy. Another child with single kidney has stable renal function but has significant rising proteinuria, which was not evident on the routine analysis 2 months before the attack of PSGN. Poststreptococcal glomerulonephritis in children is generally benign disease with low mortality in acute stage and excellent medium and long-term prognosis. We analyzed our series of PSGN patients and found that 2.6% had anomaly of the urinary tract. The unfavorable outcome was noted in children with single kidney and bilateral renal impairment.
    No preview · Article · Sep 2015 · Renal Failure
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    ABSTRACT: (Full text is available at http://www.manu.edu.mk/prilozi). Bardet-Biedl syndrome (BBS) is a multisystem genetic disorder characterized with central obesity, pigmentary retinopathy, polydactyly, mental retardation, and hypogenitalism. Renal abnormalities have been recognized as a cardinal feature of the disease with serious prognostic implication. The aim of this study was to analyze the renal status in children with BBS and to implement appropriate interventions in those with progressive course Patients and methods: The diagnosis of BBS was established on the basis of criteria proposed by Beales et al. (J Med Genet 1999). Imaging of the kidneys and urinary tract was performed with ultrasound study, Tc99mDMSA scan and a cystographic study. Twenty four hour urine collections were obtained for estimation of proteinuria and creatinine clearance. Blood pressure was monitored at clinical visits or as 24-hour ambulatory monitoring. There were 4 children (2 males, 2 females). All four children displayed abnormal kidney ultrasound and Tc99mDMSA scan resembling dysplastic kidney(s). Two of them had overt proteinuria (glomerulo-tubular pattern). Three children had normal blood pressure and glomerular filtration rate (GFR): 107, 145 and 95 ml/min/1.73m2, and the fourth had hypertension and progressive worsening of the GFR at 65 ml/min/1.73m2. Children with BBS should undergo imaging studies of the kidneys and urinary tract at initial work up; in those with renal dysplasia proteinuria, GFR and blood pressure should be regularly monitored to slow down progression to terminal renal failure. Key words: Bardet Biedl syndrome, renal dysplasia, chronic kidney disease, proteinuria, hypertension.
    No preview · Article · Jun 2015 · Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences
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    ABSTRACT: (Full text is available at http://www.manu.edu.mk/prilozi). Multiple congenital anomalies and craniofacial dysmorphism are characterizing the so-called Emanuel or supernumerary der(22)t(11;22) syndrome (OMIM609029). Mental and developmental retardation are major clinical features. The der(22) may arise from a parental balanced t(11;22)(q23;q11.2) or can be created de novo. Here we present a 2 years old boy with normal prenatal history, cyanotic at delivery and with ear anomalies, a preauricular tag, high-arched palate and micrognathia. There were neither microcephaly, nor heart or kidney defects. Psychological and motor testing at the age of 2 years confirmed significant mental and developmental delay. In addition, the child had seizures and an abnormal electroencephalogram. Cytogenetic and molecular analyses revealed a karyotype 47,XY,+der(22)t(11;22)(q23;q11.2). As parents refused further tests it could not be determined if the der(22) arose de novo or was parentally derived. Overall the present report should alert physician to offer cytogenetic and/or molecular diagnostics in comparable cases. Key words: Emanuel syndrome, congenital anomalies, derivative chromosome 22 {der(22)t(11;22)}.
    No preview · Article · Jun 2015 · Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences
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    ABSTRACT: (Full text is available at http://www.manu.edu.mk/prilozi). Wildervanck syndrome (WS) combines features of Klippel-Feil syndrome (KFS), sixth nerve palsy, and deafness. This is a case of a 23 year old woman, diagnosed with KFS (a triad of short neck, low posterior hairline and restricted neck movements) at the age of 20 days. The manifestations of the WS in this patient are severe: she has torticollis, and an extremely severe scoliosis. In addition, she is short (-3 SD; parental target height + 0.8SD) and has mixed sensorineural and conductive deafness. She also has ptosis, strabismus and a high myopia. Radiologically, there are multiple coalitions of cervical vertebrae. Intelligence is unaffected (IQ 95), but deafness, strabismus and high myopia forced her early out of school. Karyotype is 46, XX. In brief, this is a patient with severe WS and additional anomalies. Short and/or reduced parental target height is a part of WS. Key words: Wildervanck syndrome, short stature, Duane retraction syndrome, Klippel Feil anomaly, deafness, torticollis, severe scoliosis.
    No preview · Article · Jun 2015 · Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences
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    ABSTRACT: Background: Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis. Methods: We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multicenter series of 42 persons with 16p11.2 deletions. Results: We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10(-6)). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10(-6)). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis. Conclusions: Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. (Funded by the National Basic Research Program of China and others.).
    Full-text · Article · Jan 2015 · New England Journal of Medicine
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    ABSTRACT: Wildervanck syndrome (WS) combines features of Klippel-Feil syndrome (KFS), sixth nerve palsy, and deafness. This is a case of a 23 year old woman, diagnosed with KFS (a triad of short neck, low posterior hairline and restricted neck movements) at the age of 20 days. The manifestations of the WS in this patient are severe: she has torticollis, and an extremely severe scoliosis. In addition, she is short (-3 SD; parental target height + 0.8SD) and has mixed sensorineural and conductive deafness. She also has ptosis, strabismus and a high myopia. Radiologically, there are multiple coalitions of cervical vertebrae. Intelligence is unaffected (IQ 95), but deafness, strabismus and high myopia forced her early out of school. Karyotype is 46, XX. In brief, this is a patient with severe WS and additional anomalies. Short and/or reduced parental target height is a part of WS.
    No preview · Article · Jan 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multiple congenital anomalies and craniofacial dysmorphism are characterizing the so-called Emanuel or supernumerary der(22)t(11;22) syndrome (OMIM609029). Mental and developmental retardation are major clinical features. The der(22) may arise from a parental balanced t(11;22)(q23;q11.2) or can be created de novo. Here we present a 2 years old boy with normal prenatal history, cyanotic at delivery and with ear anomalies, a preauricular tag, high-arched palate and micrognathia. There were neither microcephaly, nor heart or kidney defects. Psychological and motor testing at the age of 2 years confirmed significant mental and developmental delay. In addition, the child had seizures and an abnormal electroencephalogram. Cytogenetic and molecular analyses revealed a karyotype 47,XY,+der(22)t(11;22)(q23;q11.2). As parents refused further tests it could not be determined if the der(22) arose de novo or was parentally derived. Overall the present report should alert physician to offer cytogenetic and/or molecular diagnostics in comparable cases.
    No preview · Article · Jan 2015
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    ABSTRACT: Background: Bardet-Biedl syndrome (BBS) is a multisystem genetic disorder characterized with central obesity, pigmentary retinopathy, polydactyly, mental retardation, and hypogenitalism. Renal abnormalities have been recognized as a cardinal feature of the disease with serious prognostic implication. The aim of this study was to analyze the renal status in children with BBS and to implement appropriate interventions in those with progressive course Patients and methods: The diagnosis of BBS was established on the basis of criteria proposed by Beales et al. (J Med Genet 1999). Imaging of the kidneys and urinary tract was performed with ultrasound study, Tc99 Results: There were 4 children (2 males, 2 females). All four children displayed abnormal kidney ultrasound and Tc99
    No preview · Article · Jan 2015
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    ABSTRACT: Background Atypical hemolytic uremic syndrome (aHUS) is a rare and heterogeneous disorder. The first line treatment of aHUS is plasma therapy, but in the past few years, the recommendations have changed greatly with the advent of eculizumab, a humanized monoclonal anti C5-antibody. Although recent recommendations suggest using it as a primary treatment for aHUS, important questions have arisen about the necessity of immediate use of eculizumab in all cases. We aimed to draw attention to a specific subgroup of aHUS patients with rapid disease progression and high mortality, in whom plasma therapy may not be feasible.Methods We present three pediatric patients of acute complement-mediated HUS with a fatal outcome. Classical and alternative complement pathway activity, levels of complement factors C3, C4, H, B and I, as well as of anti-factor H autoantibody and of ADAMTS13 activity were determined. The coding regions of CFH, CFI, CD46, THBD, CFB and C3 genes were sequenced and the copy number of CFI, CD46, CFH and related genes were analyzed.ResultsWe found severe activation and consumption of complement components in these patients, furthermore, in one patient we identified a previously not reported mutation in CFH (Ser722Stop), supporting the diagnosis of complement-mediated HUS. These patients were not responsive to the FFP therapy, and all cases had fatal outcome.Conclusion Taking the heterogeneity and the variable prognosis of atypical HUS into account, we suggest that the immediate use of eculizumab should be considered as first-line therapy in certain small children with complement dysregulation.
    Full-text · Article · Dec 2014 · Italian Journal of Pediatrics
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    ABSTRACT: Nephrogenic diabetes insipidus (NDI) is caused by the inability of renal collecting duct cells to respond to arginine vasopressin (AVP)/antidiuretic hormone (ADH). We present the case of a 7-year-old boy with a history of excretion of large amounts of dilute urine and polydipsia since infancy. The boy had several vomiting episodes with mild dehydration during the first 3 years of life. There was no evidence of headaches, dizziness or visual problems. He drinks between 2 and 3 L/day and has 24-hour diuresis of 2 liters, now. He has prepubertal appearance with appropriate weight [+0.85 standard deviation score (SDS)] and height (+0.15 SDS) for his age. His intelligence was also normal. The water deprivation test showed low urine osmolality after 8 hours of dehydration. After desmopressin administration, urine osmolality remained low. Serum osmolality was in the normal range for sex and age before and after desmopressin administration. This indicated a nephrogenic form of diabetes insipidus. Molecular analyses revealed a P286L [p.Pro(CCC)286Leu(CTC)] mutation in the AVPR2 gene, that was inherited from his mother. This patient is the first case with genetically confirmed X-linked inherited form of NDI in the Republic of Macedonia. Molecular analysis confirmed the clinical diagnosis and enabled genetic advice for this family.
    Full-text · Article · Dec 2014 · Balkan Journal of Medical Genetics
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    ABSTRACT: Nephrolithiasis is a prevalent condition with a high morbidity. Although dozens of monogenic causes have been identified, the fraction of single-gene disease has not been well studied. To determine the percentage of cases that can be molecularly explained by mutations in 1 of 30 known kidney stone genes, we conducted a high-throughput mutation analysis in a cohort of consecutively recruited patients from typical kidney stone clinics. The cohort comprised 272 genetically unresolved individuals (106 children and 166 adults) from 268 families with nephrolithiasis (n=256) or isolated nephrocalcinosis (n=16). We detected 50 likely causative mutations in 14 of 30 analyzed genes, leading to a molecular diagnosis in 14.9% (40 of 268) of all cases; 20 of 50 detected mutations were novel (40%). The cystinuria gene SLC7A9 (n=19) was most frequently mutated. The percentage of monogenic cases was notably high in both the adult (11.4%) and pediatric cohorts (20.8%). Recessive causes were more frequent among children, whereas dominant disease occurred more abundantly in adults. Our study provides an in-depth analysis of monogenic causes of kidney stone disease. We suggest that knowledge of the molecular cause of nephrolithiasis and nephrocalcinosis may have practical implications and might facilitate personalized treatment.
    Full-text · Article · Oct 2014 · Journal of the American Society of Nephrology
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    Ljiljana Saranac · Zoran Gucev

    Full-text · Article · May 2014
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    ABSTRACT: (Full text is available at http://www.manu.edu.mk/prilozi). Background: The genetic background of idiopathic central precocious puberty (ICPP) is not well understood, and is thought to arise from the effect of multiple genes. Familial ICPP have been reported suggesting the existence of monogenic causes of ICPP. The neurokinin B (NKB) system has recently been implicated in the regulation of the human reproductive axis. In humans, NKB and its receptor are encoded by the TAC3 and TACR3 genes, respectively. Mutations in these genes have been suggested to be causative for ICPP. Methods: ICPP was defined by pubertal onset before 8 yrs of age in girls, and a pubertal LH response to GnRH testing. Twenty eight girls with ICPP were included in the study (age at diagnosis was 5.72 ± 2.59; bone age, 6.12 ± 2.81, height at the start of treatment, 0.90 ± 1.48 SD). LHRH test was performed and was pubertal in all subjects (LH 20.35 ± 32.37 mIU/ml; FSH 23.32 ± 15.72 mIU/ml). The coding regions of TAC and TACR3 were sequenced. Results: No rare variants were detected in TAC and TACR3 in the 28 subjects with ICPP. Conclusions: We confirmed that mutations in TAC and TACR3 are not a common cause for ICPP. Key words: TAC, TACR3, idiopathic central precocious puberty, timing of puberty.
    No preview · Article · May 2014 · Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences
  • M Polenakovic · Z Gucev · V Tasic
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    ABSTRACT: (Full text is available at http://www.manu.edu.mk/prilozi). In Europe Rare Disease (RD) is the one which affects less than 1/2000, in the USA 1/1250, while in Japan RD is the one that affects fewer than 1/50,000 patients. EU estimates that 5-8000 distinct rare diseases affect 6-8% of the Population. The impact of rare diseases in the health systems is impresssive: at least 3 million patients in the UK, 4 million in Germany, and between 27 and 36 million EU citizens. There is not a precise register for rare diseases in the Republic of Macedonia. Rare diseases are becoming increasingly important as possible targets of new forms of treatment, as a valuable source of a novel insight in fundamental lows of biology, and in the specific mechanisms of many diseases. Molecular methods have created a better diagnosis and oftentimes treatment. Rare diseases pose significant problem for the patients, since their problems are often not recognized by the medical community and shunned by the health insurance. The cumulative costs of diagnosis and treatment of rare diseases is significant for any society and oftentimes not acceptable for developing countries. Key words: rare disease, molecular diagnosis, therapy.
    No preview · Article · May 2014 · Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences
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    ABSTRACT: Introduction and Aims: Autosomal recessive polycystic kidney disease (ARPKD) occurs in 1:20,000 live births and is the most common cystic kidney disease in childhood. Since kidney and liver manifestations progress differently in ARPKD, the decision of the right type of transplantation may be challenging. Most often kidney-alone transplantation (KT) is performed first, followed by liver transplantation (LT) or directly combined liver kidney transplantation (CLKT). The choice for CLKT is more and more discussed because (1) 64-80% of the mortality occurring in ARPKD with KT patients is attributed to cholangitis/sepsis related to liver disease; (2) liver allograft is immunologically protective of the kidney graft and (3) CLKT from the same donor probably provides better long-term. However, there is no consensus yet and long-term outcome data are scarce. In the present study, we aimed to analyse the characteristics and outcomes of children with ARPKD of the ESPN/ERA-EDTA registry and compare the outcome of the different transplantation strategies. Methods: 239 incident ARPKD patients were identified from the ESPN/ERA-EDTA registry who started RRT since 1995. Data included date of birth, gender, age at RRT, treatment modality of RRT, type of transplantation (KT or CLKT), changes in RRT modality during follow-up, survival and cause of death. Results: Mean age at start of RRT was 12.8 and 11.4 years in males and females respectively. Five year patient survival on RRT was 88.1%. Patients starting RRT before the age of 1 had a 20% lower 5-year survival (72.9%). Twenty nine patients died and the causes of death were infection (28%), cardiovascular disease (16%), hemorrhage (6.9%), and unknown (31%). There were 197 transplantations among 179 incident patients. Median age at time of the first transplantation was 9.3 years (IQR 3.9 to 13.6), which took place after a median of 0.4 years on dialysis (IQR 0.0-1.3). Twenty three patients (13%) received a CLKT, while 123 (69%) received a KT and in 33 (18%) the type of transplantation was unknown. There was a significant difference in 5-year patient survival according to the type of transplantation (78.6% for CLKT vs. 96.2% for KT) (p=0.03). Five year death censored renal graft survival was 74.3% (71.5% and 77.0% for CLKT and KT respectively p=0.83). There were 18 patients with at least 2 transplantations (1 patients received 3). Renal graft survival tended to be worse for the second as compared to the first renal allograft (HR 1.56 95%CI 0.71 to 3.43). Conclusions: The need for RRT in the first year of life for ARPKD adversely impacts survival. CLKT is a significant risk factor for mortality on short-term, and is not associated with better 5-year graft survival. Long term follow-up data are needed to better delineate the best transplantation strategy.
    Full-text · Article · May 2014 · Nephrology Dialysis Transplantation
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    ABSTRACT: Somatic mutations in the phosphatidylinositol/AKT/mTOR pathway cause segmental overgrowth disorders. Diagnostic descriptors associated with PIK3CA mutations include fibroadipose overgrowth (FAO), Hemihyperplasia multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal (CLOVES) syndrome, macrodactyly, and the megalencephaly syndrome, Megalencephaly-Capillary malformation (MCAP) syndrome. We set out to refine the understanding of the clinical spectrum and natural history of these phenotypes, and now describe 35 patients with segmental overgrowth and somatic PIK3CA mutations. The phenotypic data show that these previously described disease entities have considerable overlap, and represent a spectrum. While this spectrum overlaps with Proteus syndrome (sporadic, mosaic, and progressive) it can be distinguished by the absence of cerebriform connective tissue nevi and a distinct natural history. Vascular malformations were found in 15/35 (43%) and epidermal nevi in 4/35 (11%) patients, lower than in Proteus syndrome. Unlike Proteus syndrome, 31/35 (89%) patients with PIK3CA mutations had congenital overgrowth, and in 35/35 patients this was asymmetric and disproportionate. Overgrowth was mild with little postnatal progression in most, while in others it was severe and progressive requiring multiple surgeries. Novel findings include: adipose dysregulation present in all patients, unilateral overgrowth that is predominantly left-sided, overgrowth that affects the lower extremities more than the upper extremities and progresses in a distal to proximal pattern, and in the most severely affected patients is associated with marked paucity of adipose tissue in unaffected areas. While the current data are consistent with some genotype-phenotype correlation, this cannot yet be confirmed. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Apr 2014 · American Journal of Medical Genetics Part A
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    ABSTRACT: Context: Loss-of-function mutations in makorin ring finger 3 (MKRN3), an imprinted gene located on the long arm of chromosome 15, have been recognized recently as a cause of familial central precocious puberty (CPP) in humans. MKRN3 has a potential inhibitory effect on GnRH secretion. Objectives: To investigate potential MKRN3 sequence variations as well as copy number and methylation abnormalities of the 15q11 locus in patients with apparently sporadic CPP. Setting and participants: We studied 215 unrelated children (207 girls and 8 boys) from three University Medical Centers with a diagnosis of CPP. All but two of these patients (213 cases) reported no family history of premature sexual development. First-degree relatives of patients with identified MKRN3 variants were included for genetic analysis. Main Outcome Measures: All 215 CPP patients were screened for MKRN3 mutations by automatic sequencing. Multiplex ligation-dependent probe amplification was performed in a partially overlapping cohort of 52 patients. Results: We identified five novel heterozygous mutations in MKRN3 in eight unrelated girls with CPP. Four were frameshift mutations predicted to encode truncated proteins and one was a missense mutation, which was suggested to be deleterious by in silico analysis. All patients with MKRN3 mutations had classical features of CPP with a median age of onset at 6 years. Copy number and methylation abnormalities at the 15q11 locus were not detected in the patients tested for these abnormalities. Segregation analysis was possible in 5 of the 8 girls with MKRN3 mutations; in all cases, the mutation was inherited on the paternal allele. Conclusions: We have identified novel inherited MKRN3 defects in children with apparently sporadic CPP, supporting a fundamental role of this peptide in the suppression of the reproductive axis.
    Full-text · Article · Mar 2014 · The Journal of Clinical Endocrinology and Metabolism
  • Z Gucev · V Tasic · M Polenakovic
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    ABSTRACT: The Second meeting on Rare Diseases in South Eastern Europe (SEE) was held in Skope, Macedonia on November 15-16, 2013. Objective and main data: Rare diseases (RD) are a major problem in developed and especially in countries without affluence. 6-8% of every population suffers from RD. The cumulative effect of RDs on the health system of a country is increasing. Diagnosis often remains a challenge and requires international collaboration. Treatment in diseases for which medication exist is often inaccessible to patients because of the high costs. All countries of SEE need screening programs that address more diseases. Patient organizations play a major role in increasing awareness and providing the needed pressure on society to treat treatable RDs. On the other hand, RDs are frequently a source of valuable new molecular insights not only on mechanisms of their etiology and pathology, but sometimes provide an insight on mechanisms of frequent diseases in man. Further efforts are needed in improving all the RD aspects mentioned.
    No preview · Article · Mar 2014 · Pediatric endocrinology reviews: PER
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    ABSTRACT: Introduction: The tricho-rhino-phalangeal syndrome type III (TRPS III) is a rare autosomal dominantly inherited condition. The main clinical features are sparse and slow-growing hair and nails, a pear-shaped nose with a bulbous tip, elongated and flat philtrum, thin upper lip, cone-shaped epiphyses of the phalanges, and short stature. All patients have a point mutation in the TRPS1 gene. Case report: In this paper, we present a 13-year-old female with the typical clinical features of TRPS III, extreme growth retardation, severe deformities of both proximal radii resulting in limited extension of the elbows, and chronic renal failure (CRF) in addition. Molecular diagnostics revealed a missense mutation in exon 6 of TRPS1 that she inherited from her father who is also affected with TRPS III, but does not have CRF. In the index patient, the CRF was found to be due to bilateral renal hypodysplasia (RHD). Conclusion: Beside the renal dysplasia, the girl had severe deformities of the proximal radii - findings which have not been reported so far in TRPS III.
    No preview · Article · Feb 2014 · Renal Failure

Publication Stats

416 Citations
255.02 Total Impact Points

Institutions

  • 2008-2015
    • University Children's Hospital
      Skopie, Karpoš, Macedonia
  • 2009-2014
    • New York University Skopje
      Skopie, Karpoš, Macedonia
  • 2009-2010
    • Ss. Cyril and Methodius University
      • Faculty of Medicine
      Skopje, Opstina Karpos, Macedonia
  • 2008-2009
    • NGO Macedonia
      Skopie, Karpoš, Macedonia
  • 2006
    • PHO University Dental Clinical Centre St. Pantelejmon
      Skopie, Karpoš, Macedonia