Clinical characteristics of four children with 3M syndrome and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features of 3M syndrome and effect of growth hormone therapy.@*METHODS@#Clinical data of four children diagnosed with 3M syndrome by whole exome sequencing at Hunan Children's Hospital from January 2014 to February 2022 were retrospectively analyzed, which included clinical manifestation, results of genetic testing and recombinant human growth hormone (rhGH) therapy. A literature review was also carried our for Chinese patients with 3M syndrome.@*RESULTS@#The clinical manifestations of the 4 patients included severe growth retardation, facial dysmorphism and skeletal malformations. Two patients were found to harbor homozygous variants of CUL7 gene, namely c.4717C>T (p.R1573*) and c.967_993delinsCAGCTGG (p.S323Qfs*33). Two patients were found to harbor 3 heterozygous variants of the OBSL1 gene including c.1118G>A (p.W373*), c.458dupG (p.L154Pfs*1002) and c.690dupC (p.E231Rfs*23), among which c.967_993delinsCAGCTGG and c.1118G>A were unreported previously. Eighteen Chinese patients with 3M syndrome were identified through the literature review, including 11 cases (11/18, 61.1%) carrying CUL7 gene variants and 7 cases (7/18, 38.9%) carrying OBSL1 gene variants. The main clinical manifestations were in keeping with previously reported. Four patients were treated with growth hormone, 3 showed obvious growth acceleration, and no adverse reaction was noted.@*CONCLUSION@#3M syndrome has a typical appearance and obvious short stature. To attain accurate diagnosis, genetic testing should be recommended for children with a stature of less than -3 SD and facial dysmorphism. The long-term efficacy of growth hormone therapy for patients with 3M syndrome remains to be observed.

Lung Squamous Cell Carcinoma with EML4-ALK Fusion and TP53 Co-mutation Treated with Ensartinib: A Case Report and Literature Review / 中国肺癌杂志

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
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Diagnosis of a child with mitochondrial myopathy and cerebellar atrophy with ataxia due to compound heterozygous variants of MSTO1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with myopathy and cerebellar atrophy with ataxia.@*METHODS@#Clinical examinations and laboratory testing were carried out for the patient. The proband and the parents' genomic DNA was extracted from peripheral blood samples and subjected to trio whole-exome sequencing. Candidate variant was validated by Sanger sequencing.@*RESULTS@#The 1-year-and-8-month-old boy manifested motor developmental delay, ataxia, hypomyotonia, increased serum creatine kinase. Cranial MRI showed cerebellar atrophy with progressive aggravation. Genetic testing revealed that the patient has harbored compound heterozygous variants of the MSTO1 gene, namely c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile), which were respectively inherited from his mother and father. The former was unreported previously and was predicted to be likely pathogenic, whilst the latter has been reported previously and was predicted to be of uncertain significance.@*CONCLUSION@#The compound heterozygous c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile) variants probably underlay the disease in the proband. Above finding has enriched the spectrum of MSTO1 gene variants underlying mitochondrial myopathy and cerebellar atrophy with ataxia.

Evidence of heterozygosity and recombinant alleles in single cysts of Giardia duodenalis / Evidência de heterozigose e alelos recombinantes em cistos individualizados de Giardia duodenalis

Abstract Giardia duodenalis is divided into eight assemblages (named A to H). Isolates of assemblage A are divided into four sub-assemblages (AI, AII, AIII and AIV). While isolates of sub-assemblage AII are almost exclusively detected in human hosts, isolates of assemblage B are encountered in a multitude of animal hosts and humans. Here, we isolated single cysts of G. duodenalis from a human stool sample and found that one of them had overlaps of assemblage AII and B alleles and an unexpectedly high number of variants of the beta-giardin (Bg) and GLORF-C4 (OrfC4) alleles. In addition, one of the Bg alleles of that cyst had a fragment of sub-assemblage AII interspersed with fragments of assemblage B, thus indicating that this allele may be a recombinant between sequences A and B. Our results are unprecedented and put a check on the statement that different assemblages of G. duodenalis represent species with different host specificities.

Resumo A espécie Giardia duodenalis é dividida em oito grupos (nomeados de A a H). Isolados do grupo A são divididos em quatro subgrupos (AI, AII, AIII and AIV). Enquanto isolados do subgrupo AII são detectados quase exclusivamente em hospedeiros humanos, isolados do subgrupo B são encontrados em uma grande variedade de hospedeiros entre animais e humanos. Neste trabalho, foi constatado que, dentre diversos cistos individualizados de G. duodenalis provenientes de fezes de origem humana, um cisto continha os alelos AII e B e um número inesperado de variantes de alelos codificadores de beta giardina e GLORF-C4. Ainda, um dos alelos beta giardina desse cisto possuía fragmentos AII intercalando um fragmento B, indicando que esse alelo pode ser um recombinante entre alelos AII e B. Os resultados aqui apresentados são inéditos e colocam em dúvida o conceito atual de que os diferentes grupos de G. duodenalis representam espécies distintas com diferentes graus de especificidade por hospedeiros.

Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi-System Inflammation without Infectious or Autoimmune Evidence

Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs.

Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi-System Inflammation without Infectious or Autoimmune Evidence

Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs.

Genotipos de Giardia duodenalis en muestras de niños de las guarderías del Instituto Colombiano de Bienestar Familiar y de perros en Ibagué, Colombia / Giardia duodenalis genotypes found in the Instituto Colombiano de Bienestar Familiar day care centers and dogs in Ibagué, Colombia

Introducción. Se han descrito ocho genotipos de Giardia duodenalis, del A al H. Los genotipos A y B se han aislado de humanos y de una gran variedad de mamíferos; sin embargo, los genotipos del C al H han mostrado mayor especificidad de huésped. Objetivo. Identificar los genotipos de G. duodenalis a partir de quistes obtenidos en heces de niños de las guarderías del Instituto Colombiano de Bienestar Familiar (ICBF) y de perros en Ibagué, mediante PCR-RFLP de los genes de la beta giardina y la glutamato deshidrogenasa. Materiales y métodos. Los quistes de las muestras positivas para G. duodenalis fueron sometidos a concentración; se extrajo su ADN y se efectuó el análisis de PCR-RFLP de los genes de la beta giardina y de la glutamato deshidrogenasa. Como control positivo se utilizó la cepa MHOM/CO/04/G40 procedente del Grupo de Parasitología del Instituto Nacional de Salud. Resultados. De las muestras tomadas de niños, 11/23 (48 %) correspondieron al genotipo A y, 12/23 (52 %), al genotipo B. Cuatro muestras de perros presentaron los genotipos C y D, específicos de este huésped. Conclusiones. En los niños solamente se encontraron los genotipos asociados a infecciones humanas (AII, BIII y BIV) y en los perros, los genotipos específicos para este huésped (C y D). Debido al reducido tamaño de las muestras analizadas provenientes de perros, y dado que estos no estuvieron en contacto con los niños de las guarderías del ICBF, no fue posible determinar una interacción entre el ciclo de transmisión de los humanos y el de los animales.

Introduction: Eight Giardia duodenalis genotypes (A-H) have been described to date. Genotypes A and B have been isolated from humans and a wide range of mammals; however, genotypes C-H have shown greater host specificity. Objective: Identifying G. duodenalis genotypes from cysts in faeces obtained from children attending the Instituto Colombiano de Bienestar Familiar (ICBF) day care centres and from dogs in Ibagué by PCR-RFLP targeting both the b -giardin and glutamate dehydrogenase genes. Materials and methods: Cysts from G. duodenalis positive samples were concentrated, DNA was extracted and the b -giardin and glutamate dehydrogenase genes were analysed by PCR-RFLP. The MHOM/CO/04/G40 strain was used as positive control (this was obtained from the Grupo de Parasitología at the Instituto Nacional de Salud ). Results: Of the total human samples, 11/23 (48%) were genotyped as A and 12/23 (52%) as B; PCR-RFLP revealed that four canine samples were genotypes C and D, these being host-specific. Conclusions: Only genotypes associated with human infection (AII, BIII and BIV) were found in the children and host-specific genotypes were observed in canines (C and D). No interaction could be established between animal and human transmission cycles due to the small canine sample size and as the former did not come into contact with children attending ICBF day-care centres.

A Case of Recurrent Abdominal Pain with Fever and Urticarial Eruption / 대한소화기학회지

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever and serosal, synovial, or cutaneous inflammation, caused by a dysfunction of pyrin as a result of mutation within the MEFV gene. It occurs mainly among Mediterranean and Middle Eastern populations, including Jews, Arabs, and Turks. However, FMF cases have been reported outside the Mediterranean and Middle Eastern countries in recent years. Although FMF has been relatively rare in Korea until now, proper recognition of FMF might lead to more frequent diagnoses of FMF. We experienced an interesting case, a 31-year-old Korean man who presented with recurrent abdominal pain with fever and urticarial eruption for 10 years. DNA analysis showed complex mutations (p.Leu110Pro, p.Glu148Gln) in the MEFV gene. To date, three cases have been reported, and this case of FMF with skin conditions is the first case in Korea.

Genotyping of Giardia duodenalis Isolates from Dogs in Guangdong, China Based on Multi-Locus Sequence

This study aimed to identify the assemblages (or subassemblages) of Giardia duodenalis by using normal or nested PCR based on 4 genetic loci: glutamate dehydrogenase (gdh), triose phosphate isomerase (tpi), beta-giardin (bg), and small subunit ribosomal DNA (18S rRNA) genes. For this work, a total of 216 dogs' fecal samples were collected in Guangdong, China. The phylogenetic trees were constructed with MEGA5.2 by using the neighbor-joining method. Results showed that 9.7% (21/216) samples were found to be positive; moreover, 10 samples were single infection (7 isolates assemblage A, 2 isolates assemblage C, and 1 isolate assemblage D) and 11 samples were mixed infections where assemblage A was predominant, which was potentially zoonotic. These findings showed that most of the dogs in Guangdong were infected or mixed-infected with assemblage A, and multi-locus sequence typing could be the best selection for the genotype analysis of dog-derived Giardia isolates.

Single-nucleotide polymorphisms of GSK3B, GAB2 and SORL1 in late-onset Alzheimer's disease: interactions with the APOE genotype

In this study, we investigated the associations between single-nucleotide polymorphisms in GAB2 (rs2373115), GSK3B (rs6438552) and SORL1 (rs641120) and Alzheimer's disease (AD), both alone and in combination with the APOE*4 allele.

Implications of a Chr7q21.11 microdeletion and the role of the PCLO gene in developmental delay

We report here a 4-year-old boy with global developmental delay who was referred for karyotyping and fragile X studies. A small interstitial deletion on chromosome 7 at band 7q21 was detected in all cells examined. Subsequent molecular karyotype analysis gave the more detailed result of a 6.3 Mb heterozygous deletion involving the interstitial chromosome region 7q21.11. In this relatively gene-poor region, the presynaptic cytomatrix protein, Piccolo [PCLO] gene appears to be the most likely candidate for copy number loss leading to a clinical phenotype. G-banded chromosome analysis of the parents showed this deletion was inherited from the father. Molecular karyotype analysis of the father's genome confirmed that it was the same deletion as that seen in the son; however, the father did not share the severity of his son's phenotype. This cytogenetically-visible deletion may represent another example of a chromosomal rearrangement conferring a variable phenotype on different family members

RET Fusion Genes in Korean Non-Small Cell Lung Cancer

Recently, rearranged during transfection (RET) fusions have been identified in approximately 1% of non-small cell lung cancer (NSCLC). To know the prevalence of RET fusion genes in Korean NSCLCs, we examined the RET fusion genes in 156 surgically resected NSCLCs using a reverse transcriptase polymerase chain reaction. Two KIF5B-RET fusions and one CCDC6-RET fusion were identified. All three patients were females and never smokers with adenocarcinomas. RET fusion genes were mutually exclusive from EGFR, KRAS mutations and EML4-ALK fusion. RET fusion genes occur 1.9% (3 of 156) of surgically treated NSCLC patients in Koreans.

Extensive Thrombosis in a Patient with Familial Mediterranean Fever, Despite Hyperimmunoglobulin D State in Serum: First Adult Case in Korea

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever accompanied by peritonitis, pleuritis, arthritis, or erysipelas-like erythema. It is known to occur mainly among Mediterranean and Middle Eastern populations such as non-Ashkenazi Jews, Arabs, Turks, and Armenians. FMF is not familiar to clinicians beyond this area and diagnosing FMF can be challenging. We report a 22-yr old boy who presented with fever, arthalgia and abdominal pain. He had a history of recurrent episodes of fever associated with arthalgia which would subside spontaneously or by antipyretics. Autosomal recessive periodic fever syndromes were suspected. Immunoglobulin D (IgD) level in the serum was elevated and DNA analysis showed complex mutations (p.Glu148Gln, p.Pro369Ser, p.Arg408Gln) in the MEFV gene. 3D angio computed tomography showed total thrombosis of splenic vein with partial thrombosis of proximal superior mesenteric vein, main portal vein and intrahepatic both portal vein. This is a case of FMF associated with multiple venous thrombosis and elevated IgD level. When thrombosis is associated with elevated IgD, FMF should be suspected. This is the first adult case reported in Korea.

Mediterranean fever gene mutations in greek patients with Behcet's disease / Mutacionesen el gen de la fiebre mediterránea en pacientes griegos con la enfermedadde Behçet

OBJECTIVE: It is known that clinical similarities between Behcet's disease and Familial Mediterranean Fever have led to the hypothesis of a common pathogenesis. Familial Mediterranean Fever is caused by MEFV gene mutations coding for pyrin. Therefore, we examined whether these pyrin mutations are also associated with Behcet's disease. METHODS: Molecular testing for pyrin mutations was performed in 96 unrelated Greek patients with an established diagnosis of Behcet's disease. The results were compared with an analysis for pyrin mutations in 140 unrelated healthy Greek controls. RESULTS:We found no pyrin mutations among the Behcet cases tested; this result is comparable with the control group. CONCLUSIONS: Pyrin gene mutations in Greek patients with Behcet's disease are not more common than those in the general population. This finding is not in agreement with the findings in other populations. It is suggested that screening for pyrin mutations not be included in the evaluation of Greeks suspected to have Behcet's disease.

OBJETIVO:Se sabe que las similitudes clínicas entre la enfermedad de Behçet y la fiebre mediterránea familiar han llevado a la hipótesis de una patogénesis común. La fiebre mediterránea familiar es causada por mutaciones en el gen MEFV que codifica la pirina. Por lo tanto, examinamos si estas mutaciones de la pirina se hallan también asociadas con la enfermedad de Behçet. MÉTODOS: La prueba molecular para la detección de las mutaciones de la pirina se realizó en 96 pacientes griegos no relacionados, y diagnosticados con la enfermedad de Behçet. Los resultados se compararon con un análisis de las mutaciones de la pirina en 140 controles formados por individuos griegos saludables. RESULTADOS: No se encontraron mutaciones de pirina entre los casos de Behçet sometidos a prueba. Este resultado es comparable con el grupo control. CONCLUSIONES: Las mutaciones del gen de la pirina en los pacientes griegos con la enfermedad de Behçet no son más comunes que las de la población general. Este hallazgo no concuerda con los hallazgos en otras poblaciones. Se sugiere que el tamizaje para la detección de las mutaciones de pirina no se incluya en la evaluación de pacientes griegos sospechosos de padecer la enfermedad de Behçet.

Familial Mediterranean Fever: The First Adult Case in Korea

Familial Mediterranean fever (FMF) is known to be a genetic disorder that prevalent among populations surrounding the Mediterranean Sea. Since Mediterranean fever gene (MEFV) was discovered at 1997, some cases have been reported in countries not related or close to this area like Japan. In addition it has been generally accepted that the clinical onset of FMF begins before 20 yr of age in most patients. Onset of the disease at an older age may occur but is rare. Adult-onset FMF may be a form of disease with distinct clinical, demographic and molecular characteristics. We describe a case of adult-onset FMF confirmed by DNA analysis of the MEFV gene in a Korean patient. A 32-yr-old man, who has no family history of FMF, presented with periodic fever, abdominal pain and vomiting. Though several various tests were thoroughly performed to evaluate the cause of his symptoms, there was no evidence of infectious, autoimmune or neoplastic diseases. Several gene analysis of periodic fever syndrome was finally performed and two point mutations (p.Leu110Pro, p.Glu148Gln) were identified. We confirmed the first adult case of FMF through detection of MEFV gene mutations in Korea and describe his clinical characteristics.

Familial Mediterranean Fever: The First Adult Case in Korea

Familial Mediterranean fever (FMF) is known to be a genetic disorder that prevalent among populations surrounding the Mediterranean Sea. Since Mediterranean fever gene (MEFV) was discovered at 1997, some cases have been reported in countries not related or close to this area like Japan. In addition it has been generally accepted that the clinical onset of FMF begins before 20 yr of age in most patients. Onset of the disease at an older age may occur but is rare. Adult-onset FMF may be a form of disease with distinct clinical, demographic and molecular characteristics. We describe a case of adult-onset FMF confirmed by DNA analysis of the MEFV gene in a Korean patient. A 32-yr-old man, who has no family history of FMF, presented with periodic fever, abdominal pain and vomiting. Though several various tests were thoroughly performed to evaluate the cause of his symptoms, there was no evidence of infectious, autoimmune or neoplastic diseases. Several gene analysis of periodic fever syndrome was finally performed and two point mutations (p.Leu110Pro, p.Glu148Gln) were identified. We confirmed the first adult case of FMF through detection of MEFV gene mutations in Korea and describe his clinical characteristics.

Complex genetic mechanisms in glaucoma: An overview.

Glaucomas comprise a group of hereditary optic neuropathies characterized by progressive and irreversible visual field loss and damage to the optic nerve head. It is a complex disease with multiple molecular mechanisms underlying its pathogenesis. Genetic heterogeneity is the hallmark of all glaucomas and multiple chromosomal loci have been linked to the disease, but only a few genes have been characterized, viz. myocilin (MYOC), optineurin (OPTN), WDR36 and neurotrophin-4 (NTF4) in primary open angle glaucoma (POAG) and CYP1B1 and LTBP2 in congenital and developmental glaucomas. Case-control-based association studies on candidate genes involved in different stages of glaucoma pathophysiology have indicated a very limited involvement. The complex mechanisms leading to glaucoma pathogenesis indicate that it could be attributed to multiple genes with varying magnitudes of effect. In this review, we provide an appraisal of the various efforts in unraveling the molecular mystery in glaucoma and also some future directions based on the available scientific knowledge and technological developments.

case of Henoch-Schonlein purpura with P369S mutation in MEFV gene

Henoch-Schonlein purpura [HSP] is the most common vasculitis of childhood. HSP can affect multiple organs presenting with a characteristic rash in most of the patients. Familial Mediterranean Fever [FMF] is an inherited inflammatory disease common in mediterranean populations. HSP is the most common vasculitis seen in children with FMF. A 16 year old boy was referred with history of abdominal pain lasting for 20 days. He was hospitalized and had appendectomy. Due to the persistence of his abdominal pain after surgery he was admitted to our hospital. His physical examination showed palpable purpuric rashes symmetrically distributed on lower extremities. Abdominal examination revealed periumbilical tenderness. Laboratory tests showed elevated erythrocyte sedimentation rate, C-reactive protein and fibrinogen. Urinalysis revealed microscopic hematuria and severe proteinuria. The fecal occult blood testing was positive. Based on these clinic findings, the patient was diagnosed as HSP with renal, gastrointestinal tract and skin involvement. We performed DNA analysis in our patient because he had diagnosis of vasculitis with severe symptoms and found that he was carrying heterozygote P369S mutation. Our case is noteworthy as it indicates that it may be important not to overlook presence of FMF mutations in patients with a diagnosis of severe vasculitis

Freeman-sheldon syndrome-prenatal and postnatal diagnosis.

A six-day-old girl, born to normal non-consanguineous parents presented with mask like facies with a small mouth giving a ‘whistling’ appearance. Other dysmorphic features include deep set eyes, broad nasal bridge, long philtrum and ‘H’ shaped cutaneous dimple on the chin. There was congenital windmill vane hand position and severe talipes equinovarus deformity. The above features are characteristic of Freeman-Sheldon syndrome also known as Whistling Face syndrome. Ultrasound scanning during 8th month of the pregnancy showed the fetus to have facial abnormality and bilateral clenched hand and talipes with extension contractures of knees. Provisional diagnosis of FSS was made which was confirmed after the birth. Thus all cases of Arthrogryposis during prenatal scan should be carefully looked for the facial abnormality in the fetus.

Myocilin mutations are not a major cause of primary congenital glaucoma in Iranian patients

To assess the frequency of mutations in the Myocilin [MYOC] gene in Iranian patients affected with primary congenital glaucoma [PCG]. The individuals evaluated herein are among the larger cohort of 100 patients who had previously been screened for CYP1B1 mutations. Eighty subjects carried mutations in CYP1B1, but the remaining 20 patients who did not, underwent screening for MYOC mutations for the purpose of the study. MYOC exons in the DNA were polymerase chain reaction [PCR] amplified and sequenced. Sequencing was performed using PCR primers, the ABI big dye chemistry and an ABI3730XL instrument. Sequences were analyzed by comparing them to reference MYOC sequences using the Sequencher software. Four MYOC sequence variations were observed among the patients, but none of them were considered to be associated with disease status. Three of these variations were single nucleotide polymorphisms already reported not to be disease causing, the fourth variation created a synonymous codon and did not affect any amino acid change. In this cohort, MYOC mutations were not observed in any Iranian subject with PCG. It is possible that in a larger sample, a few subjects carrying disease causing MYOC mutations could have been observed. But our results show that the contribution of MYOC to PCG status in Iran is small if any