The clinical utility of molecular karyotyping for neurocognitive phenotypes in a consanguineous population.

Al-Qattan SM1, Wakil SM1, Anazi S1, Alazami AM1, Patel N1, Shaheen R1, Shamseldin HE1, Hagos ST1, AlDossari HM1, Salih MA2, El Khashab HY3, Kentab AY2, AlNasser MN2, Bashiri FA2, Kaya N1, Hashem MO1, Alkuraya FS4.

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Abstract

Purpose:Molecular karyotyping has rapidly become the test of choice in patients with neurocognitive phenotypes, but studies of its clinical utility have largely been limited to outbred populations. In consanguineous populations, single-gene recessive causes of neurocognitive phenotypes are expected to account for a relatively high percentage of cases, thus diminishing the yield of molecular karyotyping. The aim of this study was to test the clinical yield of molecular karyotyping in the highly consanguineous population of Saudi Arabia.Methods:We have reviewed the data of 584 patients with neurocognitive phenotypes (mainly referred from pediatric neurology clinics), all evaluated by a single clinical geneticist.Results:At least 21% of tested cases had chromosomal aberrations that are likely disease-causing. These changes include both known and novel deletion syndromes. The higher yield of molecular karyotyping in this study as compared with the commonly cited 11% can be explained by our ability to efficiently identify single-gene disorders, thus enriching the samples that underwent molecular karyotyping for de novo chromosomal aberrations. We show that we were able to identify a causal mutation in 37% of cases on a clinical basis with the help of autozygome analysis, thus bypassing the need for molecular karyotyping.Conclusion:Our study confirms the clinical utility of molecular karyotyping even in highly consanguineous populations.Genet Med advance online publication 11 December 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.184.