Novel alteration in AMPD2 gene segregates with non-syndromic intellectual disability linked to MRT4 locus, conjointly responsible from Pontocerebellar hypoplasia

European Human Genetics Conference 2014, Milan, İtalya, 31 Mayıs - 03 Haziran 2014, cilt.22, sa.1, ss.140

Non-syndromic autosomal recessive intellectual disability(NS-ARID) with

genetic loci are listed with MRT numbering by Mendelian Inheritance of

Man (MIM). Since the discovery of the 􀏐irst gene in MRT1, PRSS12, in 2002,

to date a total of 34 loci and 17 genes are identi􀏐ied. Only few of these genes

are published causative in more than one family, while the rest are identi􀏐ied

in a single family that are characterized, disclosing the high heterogeneity

of the genetic basis. MRT4 was published in 2007 in an examination of a

large consanguineous family with four affected members. The linked region

at 1p21.1-1p13.3 was 6.6 megabase commencing 78 genes. Exome sequencing

of family members and 􀏐iltering variations according to the pedigree

data revealed a single point mutation c.1526C>T, in AMPD2 gene, located

at 1p13.3, altering uncharged polar amino acid threonine, at position 509,

to nonpolar methionine (p.T509M), in evolutionally conserved adenosine

deaminase domain. This variation was not found in our in house exome

sequencing of 150 Turkish individuals or in publically available SNP databases.

Furthermore, this variation is assigned to be damaging by diverse

prediction software analysis. AMPD2 plays a critical role in energy metabolism,

functioning in purine metabolism by converting AMP to IMP via salvage

pathways. Recently, deleterious mutations in AMPD2 gene are reported

in 􀏐ive families with Pontocerebellar hypoplasia (PCH) with characteristic

brain imaging. Affected individuals in our family do not carry progressive

context. We conclude that our case will expand the phenotypic spectrum of

damaging AMPD2 mutations.