A new autosomal recessive syndrome of ocular colobomas, ichthyosis, brain malformations and endocrine abnormalities in an inbred Emirati family

Abstract

We report on an inbred Emirati family of Baluchi origin with ocular colobomas, ichthyosis, and endocrine abnormalities associated with midline brain malformations and mental retardation. All affected children had ocular colobomas, developmental delay and midline brain malformations. Hypoplastic pituitary gland was present in all three investigated children. Ichthyosiform dermatitis appeared in infancy in all surviving children. Other variable features include congenital heart defects, hypertrichosis and dark skin involving the dorsum of hands and feet associated with mild degree of palmo-plantar keratoderma. Some of the features in this family overlap the CHIME (Coloboma of the eye, Heart defect, Ichthyosiform dermatosis, Mental retardation, and Ear defect) syndrome. However, several features described in CHIME syndrome were not present in these children. These include deafness, seizures, oligodontia, and hair abnormalities. Some of the features in these children also overlap with septo-optic dysplasia (SOD) but optic nerve hypoplasia, mandatory for the diagnosis of SOD, was present in one child only. We suggest that these children have a new autosomal recessive syndrome of ocular colobomas and ichthyosis.

Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3

“…4 In the family reported here, no clear abnormal transferrin mobility had been detected in two independent routine tests for CDG screening. Interestingly, in the family reported by Al-Gazali et al, 5 now also known to carry an SRD5A3 mutation, 3 repeated CDG testing had failed to detect any Total number of novel SNVs detected a 13 Total number of novel indels detected a 22…”

Phenotypic Expansion of Congenital Disorder of Glycosylation Due to SRD5A3 Null Mutation

“…It affects protein N-glycosylation, as well as the synthesis of mannose-linked glycans, C-mannosylation, and glycophospholipid anchor synthesis. SRD5A3-CDG is characterized by neurological and ophthalmological findings such as nystagmus, visual impairment, microphthalmia, cataract, coloboma (iris, chorioretinal), optic disk hypoplasia, and optic nerve hypoplasia/atrophy (Assmann et al 2001;Prietsch et al 2002;Al-Gazali et al 2008;Kahrizi et al 2009Kahrizi et al , 2011Morava et al 2009Morava et al , 2010Cantagrel et al 2010;Gr€ undahl et al 2012;Kara et al 2014;Kasapkara et al 2012).…”

Consanguinity and Dysmorphology in Arabs

“…In 2008, Al-Gazali et al [110] reported on a consanguineous Emirati family of Baluchi origin with ocular colobomas, ichthyosis, and mental retardation associated with endocrine abnormalities and midline brain malformations. Six additional families with the same phenotype have later been identified [111] .…”