Computational protocol: A mutation in KIF7 is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance

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Protocol publication

[…] In order to identify the gene for this condition, we performed whole exome sequencing on two affected siblings. Blood DNA was extracted using Qiagen reagents (Qiagen Inc., USA), then subjected to exome capture with the Agilent SureSelect Human All Exome 50 Mb kit (Agilent Technologies, Inc., USA), sequenced on an Illumina HiSeq2000 instrument (Illumina, Inc., USA), resulting in ~94% recovery at >10× coverage. GATK [] was used for variant identification and intersected with identity-by-descent blocks identified by HomozygosityMapper [,], and then filtered for homozygous variants shared between the two affected. In one affected we found 4519 homozygous variants of which 4190 were in the UTRs and therefore probably not functional. In addition, 292 of the remaining 329 variants were seen in homozygous state in families with non-overlapping phenotypes from our in-house 1000 exomes from Middle Eastern patients. Furthermore, 9 of the remaining 38 variants were present in the heterozygous state in 1% or more of the cohort (i.e. out of Hardy Weinberg equilibrium with the disease frequency). Finally, of the remaining 29 variants, only the KIF7 variant fell within the previously established linkage interval15q26 []. […]

Pipeline specifications

Software tools GATK, HomozygosityMapper
Application WES analysis
Organisms Homo sapiens
Diseases Osteochondrodysplasias, Genetic Diseases, Inborn, Acrocallosal Syndrome, Megalencephaly