PDZD8 Disruption Causes Cognitive Impairment in Humans, Mice, and Fruit Flies.

Background: The discovery of coding variants in genes that confer risk of intellectual disability (ID) is an important step toward understanding the pathophysiology of this common developmental disability.

Methods: Homozygosity mapping, whole-exome sequencing, and cosegregation analyses were used to identify gene variants responsible for syndromic ID with autistic features in two independent consanguineous families from the Arabian Peninsula. For in vivo functional studies of the implicated gene's function in cognition, Drosophila melanogaster and mice with targeted interference of the orthologous gene were used.

Uptake of prenatal genetic diagnosis and termination of pregnancy by Omani Muslim families at risk of genetic disorders: experience over a 9-year period.

Studies on the acceptance of prenatal diagnosis and termination of pregnancy for single gene disorders within Islamic societies in the Middle East are limited. A few have examined the attitudes toward pregnancy termination for fetal indications, but a dearth of published data exists on actual behavior and uptake. This study reports on all prenatal diagnosis requests for single gene disorders, from the Sultanate of Oman, over 9 years.

Coexistence of Autism Spectrum Disorders Among Three Children with Tuberous Sclerosis Complex: Case reports and review of literature.

Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous disorder inherited in an autosomal dominant manner and characterised by benign tumours in the brain and other vital organs such as the heart, eyes, kidneys, skin and lungs. Links between autism spectrum disorder (ASD) and TSC have been postulated for many decades, with TSC considered to be one of the main syndromic causes of ASD; however, precise confirmation of a relationship between these two disorders required validated diagnostic tools. Fortunately, accurate evaluation of this relationship is now possible with standardised criteria for ASD diagnosis.

Seizures as an Atypical Feature of Beal's Syndrome.

Congenital contractural arachnodactyly, commonly known as Beal's syndrome, is an extremely rare genetic disorder caused by mutations in the fibrillin-2 (FBN2) gene located on chromosome 5q23. It is an autosomal dominant inherited connective tissue disorder characterised by a Marfan-like body habitus, contractures, abnormally shaped ears and kyphoscoliosis. We report a seven-year-old Omani male who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2014 with seizures.

De Novo Duplication of 7p21.1p22.2 in a Child with Autism Spectrum Disorder and Craniofacial Dysmorphism.

The duplication of the short arm of chromosome 7 as de novo is extremely rare. The phenotype spectrum varies depending on the region of duplication. We report a case of de novo duplication of chromosomal region 7p21.

A novel mutation in DDR2 causing spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications (SMED-SL) results in defective intra-cellular trafficking.

Background: The rare autosomal genetic disorder, Spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications (SMED-SL), is reported to be caused by missense or splice site mutations in the human discoidin domain receptor 2 (DDR2) gene. Previously our group has established that trafficking defects and loss of ligand binding are the underlying cellular mechanisms of several SMED-SL causing mutations. Here we report the clinical characteristics of two siblings of consanguineous marriage with suspected SMED-SL and identification of a novel disease-causing mutation in the DDR2 gene.

A rare thyroid hormone receptor beta (THRβ) gene mutation in a 15-year-old girl with thyroid hormone resistance syndrome: a case report.

Introduction: Resistance to thyroid hormone is a rare syndrome, where although the level of thyroid hormone is elevated, the level of thyroid stimulating hormone is not suppressed. The patient in our case report is, to the best of our knowledge, the first with this syndrome identified in Oman.

Case Presentation: In one Omani family, a 15-year-old girl of Arabian origin was pre-diagnosed with resistance to thyroid hormone.

Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders.

Imprinting disorders are associated with mutations and epimutations affecting imprinted genes, that is those whose expression is restricted by parent of origin. Their diagnosis is challenging for two reasons: firstly, their clinical features, particularly prenatal and postnatal growth disturbance, are heterogeneous and partially overlapping; secondly, their underlying molecular defects include mutation, epimutation, copy number variation, and chromosomal errors, and can be further complicated by somatic mosaicism and multi-locus methylation defects. It is currently unclear to what extent the observed phenotypic heterogeneity reflects the underlying molecular pathophysiology; in particular, the molecular and clinical diversity of multilocus methylation defects remains uncertain.

Impact of BRAF, MLH1 on the incidence of microsatellite instability high colorectal cancer in populations based study.

We have identified an alternative pathway of tumorigenesis in sporadic colon cancer, involving microsatellite instability due to mismatched repair methylation, which may be driven by mutations in the BRAF gene (V600E). Colorectal cancer (CRC) is the most common cancer in the world, and African Americans show a higher incidence than other populations in the United States. We analyzed sporadic CRCs in Omani (of African origin, N = 61), Iranian (of Caucasian origin, N = 53) and African American (N = 95) patients for microsatellite instability, expression status of mismatched repair genes (hMLH1, hMSH2) and presence of the BRAF (V600E) mutation.