[Larsen syndrome: report of a case]

Larsen syndrome is a rare disease with autosomal dominant inheritance, although both autosomal dominant and recessive inheritance has been reported. It is characterized by multiple joint dislocation, peculiar face, and vertebral anomalies. We are reporting a one-year-old boy with hips and knees dislocation, talipes equinovarus, hypertelorism, depressed nasal bridge, prominent forehead. We believe that our patient is a new case of Larsen syndrome

[Study of MTHFR A1298C polymorphism as a genetic risk factor for cardiovascular disease in the Iranian population]

Two hundred and eight asymptomatic individuals from different origins of Iran were included in this study in order to assess the distribution of the MTHFR A1298C polymorphism responding for cardiovascular disease [CVD] in the general Iranian population using a novel technique reverse hybridization Strip Assay for the rapid and simultaneous detection. The test is based on multiplex PCR and hybridization to a teststrip presenting a parallel array of allele-specific oligonucleotide probes for each mutation. The prevalence of mutant MTHFR A1298C in our study population [0.42], was remarkably high. Mutant MTHFR A1298C in Iran occurred less frequently than among Europeans, but exceeded the much lower frequencies known from India and most of Asia. Here we describe the distribution of mutant allele MTHFR A1298C in different ethnicities of Iranian population and compare the results to previously reported data. Our data represent the only comprehensive study to date with respect to thrombophilic gene polymorphism in Iran

[Clinical, radiological and molecular diagnosis of autosomal dominant Larsen syndrome: report of a large Iranian family]

Larsen syndrome [LS] is one of the rare autosomal dominant chondrodystrophias, characterized by multiple dislocations of the large joints, midfacial hypoplasia, and cleft palate. Recently it has been known that some missense mutations or small in-frame deletions in the gene Filamin B [FLNB] may cause autosomal dominant Larsen syndrome. Filamin B gene encodes a very important cytoskeletal protein named filamin B. This protein has central role on development of inter-cellular connective tissue, joint cartilage, and vertebral segmentation and development. In this article, we report a large Iranian pedigree including about 30 affected individuals to autosomal dominant Larsen syndrome in four subsequent generations. After ascertaining Larsen syndrome by clinical and radiological studies, in some of the available individuals of different branches of the pedigree, molecular analysis by dHPLC, direct sequencing, and endonuclease digestion methods have been carried out to detect responsible mutations in filamin B gene. We detected a point mutation on nucleotide 679 [679G>A] leading to substitution of glutamic acid instead of lysine in amino acid number 227 [E227K]. The mutation is one of the recurrent missense mutations that have been reported before in several families. In this pedigree, we found variable phenotypes according to the severity and spectrum of the symptoms

Deletions in the survival motor neuron gene in Iranian patients with spinal muscular atrophy

<p><b>INTRODUCTION</b>Spinal muscular atrophy (SMA) is a common neuromuscular disorder with progressive paralysis caused by the loss of alpha-motor neurons in the spinal cord. The survival motor neuron (SMN) protein is encoded by 2 genes, SMN1 and SMN2. The most frequent mutation is the biallelic deletion of exon 7 of the SMN1 gene. In SMA, SMN2 cannot compensate for the loss of SMN1, due to the exclusion of exon 7. The aim of our study was to estimate the frequency of the common SMN1 exon 7 deletion in patients referred to our centre for carrier detection and prenatal diagnosis.</p><p><b>MATERIALS AND METHODS</b>We performed the detection of exon 7 deletion of the SMN1 gene for the affected patients and fetuses suspected to have SMA.</p><p><b>RESULTS</b>Of 243 families, 195 were classified as SMA type I, 30 as type II, and 18 as type III according to their family histories. The analysis of exon 7 deletion among living affected children showed that 94% of the patients with SMA type I, 95% with type II families and 100% with type III had homozygous deletions. Of the prenatal diagnoses, 21 (22.8%) of the 92 fetuses were found to be affected and these pregnancies were terminated.</p><p><b>CONCLUSIONS</b>The homozygosity frequency for the deletion of SMN1 exon 7 for all 3 types was (94%), similar to those of Western Europe, China, Japan and Kuwait.</p>

[ new case of acro-cardio-facial syndrome: further evidence for clinical variability]

We are reporting a 25 year old man with minor facial and genital anomalies and bilateral ectrodactyly. His parents are first cousins and are both healthy. Facial manifestations included hypertelorism, short down-slanted palpebral fissures, small low-set ears and high forehead. Genital anomalies were undescended right testicle, micropenis and hypospadias. There were four fingers in both hands with a feature of cleft deformity and bone hypoplasia. His sister died four days after birth with severe limb defects and imperforate anus

[Aspects of Greig cephalopolysyndactyly syndrome in a patient with 7pl3pl5 deletion]

A 1-month-old infant with some aspects of Greig cephalopolysyndactyly syndrome [GCPS] and additional features is described. High-resolution chromosomal analysis showed a de novo interstitial deletion of chromosome 7p with breakpoints located at p13 and p15. Our case has some additional features of GCP syndrome, such a cleft palate, narrow auditory canal, umbilical hernia, inguinal hernia, hirsutism, sacral dimple and small skin tag above natal cleft. Frontal bossing, macrocephaly, and high forehead, features associated with GCP was absent in our patient. Hirsutism has been previously reported in only 5 patients with 5p13 deletion. Based on those cases, it has been suggested that the responsible gene might be located in that region. Our patient gives further evidence of this hypothesis

[Survival motor neuron gene deletions among Iranian patients with spinal muscular atrophy]

Spinal muscular atrophy [SMA] is a common neuromuscular disorder with progressive paralysis caused by the loss of alpha-motor neuron in the spinal cord. SMN is encoded by two genes, SMN1 and SMN2, which essentially differ by a single nucleotide in exon 7. The most frequent mutation is biallelic deletion of exon 7 of the SMN1 gene. A small percentage of SMA patients present compound heterozygosity with a point mutation on one allele and deletion on the other. In the remaining cases, the disease is unlikely to be related to SMN1 defects. In spinal muscular atrophy [SMA], SMN2 is not able to compensate for the loss of SMN1 due to exclusion of exon 7. The aim of our study was to estimate the frequency of the common exon 7 SMN1 deletion in the families who referred to our center for carrier detection and prenatal diagnosis. Between March 1999 and March 2006, one hundred sixty seven families with history of at least one affected member were referred to us. We performed detection of deletion exon 7 SMN1 for the patients and carrier detection for their parents, prenatal diagnosis in subsequent pregnancies to couples who previously had an affected child became possible [63 prenatal diagnosis]. From 167 families, 139 categorized in type I of the disease, 21 in type II, and 7 in type III. Carrier detection for the parents indicated that in 96 families with history of affected member with type I SMA both parents carried the deletion in exon 7 and in 20 families, one of the parents was carrier. These rates were 16 to 1 for SMA type II, and 3 to 2 for type III SMA. Sixty-four children affected with SMA were studied, 58 of them were found to be homozygous for the loss of exon 7 of the SMN1 gene, except two patients who were heterozygote for exon 7 deletion [frequency of homozygocity: 90.7%]. Eleven of sixty-three [17.5%] fetal samples were found to be affected and these pregnancies were terminated. The molecular analysis of the biallelic exon 7 of the SMN1 deletion is a standard and reliable test in cases of SMA

[Seventeen years experience in precise diagnosis and prenatal diagnosis of mucopolysaccharidoses [MPS]]

Upon a scientific collaboration, families having affected offspring suspected for MPS disease were enzymaticaly analyzed. In 82 families the deficit enzymes were detected. Seventy prenatal diagnosis for parous at risk were performed, revealing 53 unaffected and 17 affected fetuses. All families with affected fetuses opted for pregnancy termination. The prenatal result of unaffected newborns confirmed the prenatal diagnosis findings. The summary of clinical findings and epidemiological distribution of MPS disorders and PND results are presented in this short report

Peroxisomal disorders: our experiments and physician guide

Peroxisomes are responsible for a number of very important metabolic reactions, including synthesis of glycerol ethers, shortening very long chain fatty acids [VLCFAs; C24:O and C26:O], and oxidation of the side chain of cholesterol needed for bile acid production. Peroxisomal biogenesis disorders [PBDs] are genetically and phenotypically related disorders that involve enzymatic activities of peroxisomes. They are rare mostly autosomal recessive diseases characterized by multi-systemic structural and functional abnormalities. A number of biochemical abnormalities have been described in PBD patients including decreased levels of plasmalogens, and increased levels of VLCFAs and cholestanoic acid derivatives. More than 25 different entities have been diagnosed and reported in the last two decades. The most severe condition is the Zellweger syndrome, a condition due to the absence of functional peroxisomes. Affected patients are severely ill, and show multiple congenital anomalies and neurological aberrations. Chondrodysplasia punctata is another example; they are genetically heterogeneous group of dysplasias having stippling of the epiphyses in infancy as a common feature. Peroxisomal abnormalities only found in the rhizomelic type I. There are specific biochemical tests for evaluating peroxisomal functions. The diagnoses on suspected cases can now be confirmed precisely by detailed biochemical evaluation and molecular analysis in some metabolic centers. Accumulation of certain VLCFAs [C24:0, and C26:0]; deficiency of plasmalogens, and elevation of phytanic acid are some of them. Herein we report 10 Iranian families with 15 affected cases of Zellweger syndrome and rhizomelic type I chondrodysplasia punctata [RCDP I]

[Genetic analysis of FMF in a small village with high frequency in North West of Iran]

Familial Mediterranean Fever [FMF] is an inherited inflammatory disorder which caused by mutations in the MEFV gene. The disease is common among Turks, Armenians and Arabs, whereas no data from the neighbor countries is available. We studied an 8 years old boy with periodic fever and recurrent abdominal pain. Genotype analysis was performed by reverse-hybridization for 12 most frequent variants. Result indicated the patient and several individuals in the family were compound heterozygote or homozygote for the mutations. Genetic analysis for the other individuals without any clinical features in the village showed an allelic frequently of 22%, which is the highest rate reported to date

[Genetic analysis for Gaucher disease in two Iranian families]

Gaucher disease [GD] is one of the lysosomal storage disorders which inherited in an autosomal recessive mode. There is no data available from the incidence of the disease in Iran. The aim of the study was to determine the type of mutations and clinical information in Iranian patients. After detection of the mutations for the parents we performed prenatal diagnosis for the pregnancies at risk. The result of genetic analysis for two families was similar and indicated L444P mutation for both diagnoses. The result indicated that the two fetuses were normal for the disease and inherited L444P mutation in heterozygote status