Further Clinical and Molecular Delineation of Xp11.22 Deletion Syndrome: A Case Report.

Intellectual disability (ID) is the most common diagnosis noted among children with genetic disorders. It causes social and economic burden to families and communities. The genetic causes are not completely understood, and there is significant heterogeneity. Recently, a new chromosomal X-linked syndrome was reported to cause ID. Four males were described from three families with ID, developmental delay, hypotonia, joint hypermobility, and relative macrocephaly. They all carried small, overlapping Xp11.22 deletions. To date, the described smallest region of overlapping deletion at this locus spanned ~ 430 kb) and included four genes (CENPVL1, CENPVL2, MAGED1, and GSPT2), which are proposed as the main drivers of the phenotype. We describe a male patient who matches the phenotype and contributes to defining a narrow phenocritical region at Xp11.22. We propose that GSPT2 loss-of-function might be the probable cause of the phenotypic features seen in these patients.

Novel mutation in wolcott-rallison syndrome with variable expression in two omani siblings.

Wolcott-Rallison syndrome (WRS) is an autosomal recessive disease, characterized by neonatal or early-onset non-autoimmune insulin-dependent diabetes. WRS, although rare, is recognized to be the most frequent cause of neonatal-onset diabetes. The majority of reported patients are from consanguineous families. Several mutations with variable expression of the syndrome are reported. Here we describe a six-year-old boy with WRS who was evaluated at Sultan Qaboos University Hospital and was found to have a novel homozygous nonsense mutation in the EIF2AK3 gene. His younger sister also had WRS but with milder expression. The mutation exhibited different clinical characteristics in the siblings proving that WRS patients phenotypic variability correlates poorly to genotype. This is the first case report of two Omani children with WRS and a report of a novel mutation.