novel variant in the endothelin-converting enzyme-like 1 [ECEL1] gene in an Emirati child

Objective: The aim of this work was to report a case of an Emirati child who presented with developmental delay and multiple congenital abnormalities that are consistent with distal arthrogryposis type 5D

Clinical Presentation and Intervention: The clinical presentation comprised contractures of the shoulders, elbows, and knees in addition to camptodactyly and neck pterygium. The facial dysmorphic features noted include ptosis and microretrognathia. Importantly, left orchidopexy was also observed and corrected surgically. Whole exome sequencing revealed that the patient is homozygous for the novel c.1184+1G>T variant in endothelin-converting enzyme-like 1 [ECEL1]

Conclusion: This is a case of a novel homozygous splice site mutation in the ECEL1 gene in a child with a phenotype consistent with distal arthrogryposis type 5D. The child was born to consanguineous Emirati parents heterozygous for the novel ECEL1 mutation

Marinesco-sjogren syndrome in an Emirati child with a novel mutation in SIL1 affecting the 5' untranslated region

Objective: The aim of this study was to report clinical and molecular findings in an Emirati child with Marinesco-Sjogren syndrome born to consanguineous parents

Clinical Presentation and Intervention: The child presented with developmental delay, ataxia, bilateral cataracts, and dysmorphic craniofacial features, along with cerebellar atrophy. Sequencing of the SIL1 gene revealed a novel homozygous large indel mutation that was predicted to abrogate part of the 5' untranslated region [UTR] and the first 30 amino acids of the protein

Conclusion: This was a case of mutation in SIL1 that affected the 5' UTR, translation initiation site and the endoplasmic reticulum-targeting signal sequence. Further studies will be needed on the functional delineation of the mutation. aracts, and intellectual disability [1] . Although these are the main symptoms, there are a range of other clinical features associated with this condition in some families, including hypogonadotropic hypogonadism, skeletal abnormalities, and microcephaly [2]. The only gene known so far to be associated with MSS, SIL1, was discovered by two independent teams simultaneously [2, 3]. SIL1 plays a vital role in the translocation of proteins into the endoplasmic reticulum [ER]. Studies in mouse models have shown a function for SIL1 as a nucleotide exchange factor for the ER chaperone protein BiP, as well as in ER stressinduced apoptotic signaling and the ER-associated degradation [ERAD] pathway, again via its interaction with BiP [4, 5] . Hence, we report a consanguineous Emirati family affected with MSS with a novel mutation in the SIL1 gene

study in pleiotropy - Jalili syndrome

Jalili syndrome, first described 25 years ago in a Palestinian family, is a rare autosomal recessive genetic disorder that is characterized by the comorbid appearance of cone-rod dystrophy [CRD] and amelogenesis imperfecta. To date, 71 patients with this condition belonging to 17 different families have been reported worldwide. Studies into the molecular aetiology of Jalili syndrome have identified mutations in the CNNM4 gene, located on chromosome 2q11. Other members of this protein family have been shown to be involved in mineral transport. We postulate a role for the CNNM4 protein in metal ion transport and homeostasis and especially in the transport of magnesium ions. Mutations in the gene could interfere with the depolarization process of retinal cells, as well as in the dental biomineralization process. We also show that mutations localized to the transmembrane domain of this protein result in more severe phenotypes of the syndrome, indicating an important function for this domain, probably as a transmembrane channel for metal transport. Jalili syndrome offers an example of how a single mutation in a gene is capable of affecting two independent traits by causing a defect in a single protein that carries out essentially the same function in two different tissue types. Given that 274inherited disorders, almost exclusively reported in Arab families, have no defined genetic aetiologies as yet, and with the increasing trend of pome-wide association studies in the region, it is highly plausible that more conditions will be assumed to be manifestations of pleiotropy