Genes, Vol. 12, Pages 731: Modifier Genes in Microcephaly: A Report on WDR62, CEP63, RAD50 and PCNT Variants Exacerbating Disease Caused by Biallelic Mutations of ASPM and CENPJ

Genes, Vol. 12, Pages 731: Modifier Genes in Microcephaly: A Report on WDR62, CEP63, RAD50 and PCNT Variants Exacerbating Disease Caused by Biallelic Mutations of ASPM and CENPJ Genes doi: 10.3390/genes12050731 Authors: Ehtisham Ul Haq Makhdoom Syeda Seema Waseem Maria Iqbal Uzma Abdullah Ghulam Hussain Maria Asif Birgit Budde Wolfgang Höhne Sigrid Tinschert Saadia Maryam Saadi Hammad Yousaf Zafar Ali Ambrin Fatima Emrah Kaygusuz Ayaz Khan Muhammad Jameel Sheraz Khan Muhammad Tariq Iram Anjum Janine Altmüller Holger Thiele Stefan Höning Shahid Mahmood Baig Peter Nürnberg Muhammad Sajid Hussain Congenital microcephaly is the clinical presentation of significantly reduced head circumference at birth. It manifests as both non-syndromic—microcephaly primary hereditary (MCPH)—and syndromic forms and shows considerable inter- and intrafamilial variability. It has been hypothesized that additional genetic variants may be responsible for this variability, but data are sparse. We have conducted deep phenotyping and genotyping of five Pakistani multiplex families with either MCPH (n = 3) or Seckel syndrome (n = 2). In addition to homozygous causal variants in ASPM or CENPJ, we discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT—genes already known to be associated with neurological disorders. MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic ...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research