De novo Mutation in CACNA1S Gene in a 20-Year-Old Man Diagnosed with Metabolic Myopathy.

The calcium channel, voltage-dependent, L-type, alpha 1S subunit (CACNA1S) gene encodes a skeletal Ca2+ channel which is involved in calcium-dependent processes such as muscle contraction and neurotransmitter release. Mutations in this gene have been accompanied by hypo- and normokalemic periodic paralysis, thyrotoxic periodic paralysis, and susceptibility to malignant hyperthermia. We report the clinical and genetic findings in a patient diagnosed with metabolic myopathy who had episodic attacks of muscle pain and weakness but with no family background of the disease.

Barber-Say Syndrome and Ablepharon-Macrostomia Syndrome: A Patient's View.

Barber-Say syndrome (BSS) and ablepharon-macrostomia syndrome (AMS) are infrequently reported congenital malformation disorders caused by mutations in the gene. Both are characterized by abnormalities in ectoderm-derived structures and cause a very unusual morphology of mainly the face in individuals with otherwise normal cognition and normal physical functioning. We studied the impact that the presence of BSS and AMS has on psychosocial functioning of affected individuals and their families, using their point of view to start with.

Analysis of Copy Number Variations in Patients with Autism Using Cytogenetic and MLPA Techniques: Report of 16p13.1p13.3 and 10q26.3 Duplications.

Autism is a common neuropsychiatric disorder affecting 1 in 68 children. Copy number variations (CNVs) are known to be major contributors of autism spectrum disorder (ASD). There are different whole genome or targeted techniques to identify CNVs in the patients including karyotyping, multiplex ligation-dependent probe amplification (MLPA) and array CGH.

Familial Case of Pelizaeus-Merzbacher Disorder Detected by Oligoarray Comparative Genomic Hybridization: Genotype-to-Phenotype Diagnosis.

. Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive hypomyelinating leukodystrophy characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay. It is caused by mutation in the PLP1 gene.

Copy Number Variants in Patients with Autism and Additional Clinical Features: Report of VIPR2 Duplication and a Novel Microduplication Syndrome.

Autism is a common neurodevelopmental disorder estimated to affect 1 in 68 children. Many studies have shown the role of copy number variants (CNVs) as a major contributor in the etiology of autism with the overall detection rate of about 10-15 % and over 20 % when syndromic forms of autism exist. In this study, we used array CGH to identify CNVs in 15 Iranian patients with autism.

Analysis of in pediatric and adult glaucoma and other ocular phenotypes.

Purpose: The gene encodes an enzyme that is a member of the cytochrome P450 superfamily. Mutations in have been mainly reported in recessive pediatric ocular phenotypes, such as primary congenital glaucoma (PCG) and congenital glaucoma with anterior segment dysgenesis (CG with ASD), with some likely pathogenic variants also identified in families affected with adult-onset primary open angle glaucoma (POAG).

Methods: We examined in 158 pediatric patients affected with PCG (eight), CG with ASD (22), CG with other developmental ocular disorders (11), juvenile glaucoma with or without additional ocular anomalies (26), and ASD or other developmental ocular conditions without glaucoma (91); in addition, a large cohort of adult patients with POAG (193) and POAG-negative controls (288) was examined.

Profiling Fanconi Anemia Gene Mutations among Iranian Patients.

Background: Fanconi anemia (FA) is a rare genetic syndrome characterized by developmental defects, bone marrow failure, and a high cancer risk. FA is usually inherited as an autosomal recessive condition. This disease is genetically heterogeneous and mutations in 16 different genes have been identified in FA patients to date.

Novel CFTR Mutations in Two Iranian Families with Severe Cystic Fibrosis.

Background: Cystic fibrosis (CF) is a common autosomal recessive disorder that affects many body systems and is produced by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF is also the most frequently inherited disorder in the West. The aim of this study was to detect the mutations in the CFTR gene in two Iranian families with CF.

Mutation in TWINKLE in a Large Iranian Family with Progressive External Ophthalmoplegia, Myopathy, Dysphagia and Dysphonia, and Behavior Change.

Background: TWINKLE (c10orf2) gene is responsible for autosomal dominant progressive external ophthalmoplegia (PEO). In rare cases, additional features such as muscle weakness, peripheral neuropathy, ataxia, cardiomyopathy, dysphagia, dysphonia, cataracts, depression, dementia, parkinsonism, and hearing loss have been reported in association with heterozygous mutations of the TWINKLE gene.

Methods: We have studied a large Iranian family with myopathy, dysphonia, dysphagia, and behavior change in addition to PEO in affected members.

Carrier Testing in Known Autosomal Recessive Intellectual Disability Genes in an Iranian Healthy Individual Using Exome Sequencing.

Background: Intellectual Disability (ID) is one of the most common disabling impairments worldwide. Autosomal recessive ID (ARID), a genetically heterogeneous disorder, is more common in countries such as Iran where the rate of consanguineous marriages is high. Considering the social-economic burden of ARID in our country, it is crucial to find out whether couples who are cousins are carriers for disease causing mutations, in order to prevent the birth of an affected child.

Using immunofluorescence (antigen) mapping in the diagnosis and classification of epidermolysis bullosa: a first report from Iran.

Background: Immunofluorescence antigen mapping (IFM), is a newly introduced technique for diagnosis and classification of epidermolysis bullosa (EB) disease. The precise level of skin cleavage can be determined using monoclonal antibodies to EB-specific basement membrane zone protein.

Objective: To apply IFM technique in diagnosis and classification of EB and to identify utility and limitation of this method in our clinical setting.

Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability.

Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.

Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma.

Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively; however, the majority of cases lack a genetic etiology. We analyzed 28 probands affected with A/M spectrum (without mutations in SOX2/FOXE3) by whole-exome sequencing.

Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes.

Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families.

Prenatal Screening for Aneuploidies Using QF-PCR and Karyotyping: A Comprehensive Study in Iranian Population.

Background: We have investigated the efficacy of QF-PCR for the prenatal recognition of common aneuploidy and compared our findings with cytogenetic results in our laboratories.

Methods: A total of 4058 prenatal samples (4031 amniotic fluid and 27 chorionic villous samples) were analyzed by QF-PCR using several selected STR markers together with amelogenin. Results were compared to those obtained by conventional cytogenetic analysis.

Mutations in MAB21L2 result in ocular Coloboma, microcornea and cataracts.

Ocular coloboma results from abnormal embryonic development and is often associated with additional ocular and systemic features. Coloboma is a highly heterogeneous disorder with many cases remaining unexplained. Whole exome sequencing from two cousins affected with dominant coloboma with microcornea, cataracts, and skeletal dysplasia identified a novel heterozygous allele in MAB21L2, c.

Report of a patient with limb-girdle muscular dystrophy, ptosis and ophthalmoparesis caused by plectinopathy.

Mutations in plectin, a widely expressed giant cytolinker protein can lead to different diseases mostly with signs of muscular dystrophy (MD) and skin blistering. The only report of plectin-related disease without skin involvement is limb-girdle muscular dystrophy type 2Q (LGMD2Q) phenotype, showing early-onset limb-girdle muscular dystrophy symptoms with progressive manner and no cranial muscle involvement. Here, we report a non-consanguineous Iranian family with two affected sisters showing progressive limb and ocular muscle weakness.

Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway.

Neu-Laxova syndrome (NLS) is a rare autosomal-recessive disorder characterized by a recognizable pattern of severe malformations leading to prenatal or early postnatal lethality. Homozygous mutations in PHGDH, a gene involved in the first and limiting step in L-serine biosynthesis, were recently identified as the cause of the disease in three families. By studying a cohort of 12 unrelated families affected by NLS, we provide evidence that NLS is genetically heterogeneous and can be caused by mutations in all three genes encoding enzymes of the L-serine biosynthesis pathway.

Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome.

Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants.

Investigation of microdeletions in syndromic intellectual disability by MLPA in Iranian population.

Background: Intellectual Disabilities (ID), defined as a state of developmental deficit, result in significant limitation of intellect and poor adaptation behavior. A number of genetic factors can result in ID, such as chromosomal abnormalities, copy number variation, and single gene defect. Karyotyping is the routine method for detecting chromosomal abnormalities in patients with ID.

Olmsted syndrome in an Iranian boy with a new de novo mutation in TRPV3.

Olmsted syndrome (OS) is a rare congenital skin disorder characterized by palmoplantar keratoderma, periorificial hyperkeratotic lesions and alopecia. Constriction of digits, onychodystrophy and pruritus may also occur. Recently, pathogenic heterozygous mutations in TRPV3 were identified, with most cases showing de novo dominant inheritance.

Retinitis pigmentosa, cutis laxa, and pseudoxanthoma elasticum-like skin manifestations associated with GGCX mutations.

Gamma-glutamyl carboxylase (GGCX) mutations have been reported in patients with a pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, and multiple vitamin K-dependent coagulation factor deficiencies. We report on the clinical findings and molecular results in 13 affected members of two families who had a uniform phenotype consisting of (PXE)-like skin manifestations in the neck and trunk, loose sagging skin of the trunk and upper limbs, and retinitis pigmentosa confirmed by electroretinographies in 10 affected individuals. There were no coagulation abnormalities.

Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.

Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically.

Preliminary identification of hemoglobin q-iran in an Iranian family from central province of Iran by globin chain analysis on HPLC.

Many abnormal α-chain hemoglobins (Hbs) are caused by single nucleotide mutations in α1- or α2-goblin genes. One of these Hbs is Hb Q-Iran which is resulted from a point mutation at codon 75 of the α1-globin gene (Asp→His). The identification of Hb Q-Iran was observed in two members of a family from the Central Province of Iran.