POMKmutation in a family with congenital muscular dystrophy with merosin deficiency, hypomyelination, mild hearing deficit and intellectual disability

Abstract

Homozygous truncating mutations in POMK lead to CMD with secondary merosin deficiency, hypomyelination and intellectual disability. Loss of desmin suggests that failure of proper α-dystroglycan glycosylation impedes the binding to extracellular matrix proteins and also affects the cytoskeleton.

RecessiveDEAF1mutation associates with autism, intellectual disability, basal ganglia dysfunction and epilepsy

“…Autozygosity mapping was done with DNA samples of three affected (II:1, II:2, II:6) and three unaffected siblings (II:3, II:4, II:5) using the GeneChip Human Mapping 6.0 SNP array (Affymetrix), as described 5. Using HomozygosityMapper2012 (http://www.homozygositymapper.org), we delineated genetic intervals that were autozygous only in the affected individuals 6…”

Genetics and mechanisms leading to human cortical malformations

“…These genes include POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, ISPD, GTDC2, TMEM5, POMK, B4GAT1, B3GALNT2 (see Table 4) [212,213,[215][216][217][218][219][220][221][222][223][224][225]. Other mutations are rare, described in only a few patients with WWS, and include genes encoding BM constituents, such as LAMB1, LAMC3 and COL4A1, and the transmembrane and tetratricopeptide repeat containing 3 gene, TMTC3 [215,218,226], coding for a protein for which its link is currently unclear.…”

A novelTRAPPC11mutation in two Turkish families associated with cerebral atrophy, global retardation, scoliosis, achalasia and alacrima

“…DNA preparation was performed according to standard protocols using the QIAamp DNA Mini Kit (Qiagen). Homozygosity mapping was done with DNA samples of three affected patients of both families (F1.II:2, F2.II:2, F2.II:3) using the GeneChip Human Mapping 6.0 SNP array (Affymetrix), as described 20. HomozygosityMapper 2012 (http://www.homozygositymapper.org) was used to delineate genetic intervals that were homozygous for 400 SNPs in succession in the affected individuals 21.…”

“…A variant file was generated for all exons ±20 bp flanking regions using the GATK V.3.3 software package and sent to MutationTaster2 (http://www.mutationtaster.org) for the assessment of potential pathogenicity 22. Filtering options were used as described 20. All relevant variants were inspected visually using the Integrative Genomics Viewer (http://www.broadinstitute.org/igv).…”