Growth and neurodevelopmental disorder with arthrogryposis, microcephaly and structural brain anomalies caused by Bi-allelic partial deletion of SMPD4 gene.
Sunita Bijarnia MahayPuneeth H SomashekarParneet KaurSamarth KulshresthaVedam L RamprasadSakthivel MuruganSeema SudAnju ShuklaPublished in: Journal of human genetics (2021)
Neutral sphingomyelinases have an important role in generation of ceramide and phosphorylcholine from sphingomyelins which then act as secondary messengers in various signaling pathways of the cellular machinery. They function ubiquitously with a predominant role in the central nervous system. Neutral sphingomyelinase type 3, encoded by SMPD4 gene has recently been reported to cause a severe autosomal recessive neurodevelopmental disorder with congenital arthrogryposis and microcephaly. We report a 22-month-old girl having characteristic features of neurodevelopmental delay, prenatal onset growth failure, arthrogryposis, microcephaly and brain anomalies including severe hypomyelination, simplified gyral pattern and hypoplasia of corpus callosum and brain stem. In addition, she was noted to have nystagmus and visual impairment secondary to macular dystrophy and retinal pigment epithelial stippling at posterior pole. Copy number variant analysis from trio whole exome sequencing (ES) enabled identification of a homozygous 11 kb deletion encompassing exons 18-20 of SMPD 4 gene, confirming the diagnosis of SMPD4-related disorder in her.
Keyphrases
- copy number
- zika virus
- mitochondrial dna
- intellectual disability
- genome wide
- resting state
- white matter
- early onset
- dna methylation
- functional connectivity
- signaling pathway
- cerebral ischemia
- pregnant women
- genome wide identification
- autism spectrum disorder
- epithelial mesenchymal transition
- gene expression
- congenital heart disease
- transcription factor
- blood brain barrier
- cerebrospinal fluid
- cell proliferation