Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf-Hirschhorn Syndrome.

摘要: Wolf–Hirschhorn syndrome (WHS) is a complex genetic disorder caused by the loss of genomic material from short arm chromosome 4. Genotype–phenotype correlation studies indicated that genes within 4p16.3 necessary for expression core features phenotype. Within this region, haploinsufficiency WHSC1 and LETM1 thought to be major contributor pathogenesis WHS. We present clinical findings three patients with relatively small (<400 kb) de novo interstitial deletions overlap LETM1. 3D facial analysis was performed two these patients. Based on our findings, we propose hemizygosity associated phenotype characterized growth deficiency, feeding difficulties, motor speech delays. The deletion additional nearby does not result in marked increase severity features, arguing against their haploinsufficiency. absence seizures typical WHS craniofacial cohort suggest distinct or features. Altogether, results show although loss-of-function and/or contributes some WHS, required full phenotype, providing further support contiguous gene disorder.