Building: Bourbon Cataratas Convention Centre, Foz do Iguaçu
Room: Iguazu II
Date: 2014-05-05 04:45 PM – 05:00 PM
Last modified: 2014-02-09
Abstract
INTRODUCTION: The 9p13 microdeletion syndrome was recently reported in two unrelated young children with facial dysmorphism, developmental delay, short stature, and precocious puberty (Niemi et al, 2012). Autosomal dominant (VCP, TPM2) and autosomal recessive (GALT, ILIIRA) genes map within this 5 Mb region of 9p13.13. Associated phenotypes include: IBMPFD1-inclusion body myopathy with Paget disease of bone and frontotemporal dementia (VCP), distal arthrogryposis type 1/type 2B Nemaline myopathy (TPM2), galactosemia (GALT), craniosynostosis, delayed tooth eruption, and supernumerary teeth (ILIIRA). GALT and FANCG are the only two genes known to be dosage sensitive. Protein under-wrapping predicts gene dosage sensitivity.
OBJECTIVE: Describe the clinical, molecular findings in 2 children with the 9p13 microdeletion syndrome and in silico prediction of gene dosage sensitivity using protein under-wrapping analysis.
METHODS: Two unrelated young (6.5 and 10 years old) children underwent a comprehensive clinical genetic evaluation and array comparative genomic hybridization analysis.
RESULTS: A 5 Mb de novo heterozygous deletion at 9p13.3p13.1 with similar breakpoints was identified in both children on aCGH analysis. They have developmental delays, autism, overlapping facial dysmorphism, panhypopituarism, short stature and metopic suture synostosis.
CONCLUSION: GALT and IL11RA are dosage sensitive genes since their haplosufficiency causes low GALT enzyme activity identifiable on routine metabolic newborn screening and metopic suture synostosis respectively. However, haploinsufficiency of VCP and TPM2 genes was not sufficient to produce related phenotypes suggesting that they are dosage insensitive. We also propose that a hypopituitarism related gene maps within this region.