A homozygous 237-kb deletion at 1p31 identified as the locus for midline cleft of the upper and lower lip in a consanguineous family

作者：Yildirim Yeserin; Kerem Metin; Koroglu Cigdem; Tolun Aslihan^*

来源：European Journal of Human Genetics, 2014, 22(3): 333-337.

DOI：10.1038/ejhg.2013.138

• facial midline defect
• cleft lip
• orofacial clefting

Orofacial clefts are congenital defects that vary widely in type and severity, and can occur in isolation or in association with a variety of other defects. Herein, we describe a consanguineous family afflicted with a unique form of orofacial clefting manifesting as a facial midline defect that also involves mandibular and maxillary structures. All four affected sibs had median clefts of the upper and lower lips, tooth misalignment, and poor oral hygiene. Linkage analysis of 17 family members identified a 15.3-Mb pair recessive locus at 1p31 with a LOD score of 3.63. To the best of our knowledge, this is, to date, the first locus reported for facial midline clefting and the first recessive locus for an isolated orofacial defect. The locus harboured a novel intergenic deletion of 273 164 bp, for which all fully affected sibs were homozygous. We did not note any potentially pathogenic gene variant at the 1p31 locus via exome-sequencing analysis. The identified deletion could be harbouring a regulatory element for the gene associated with the orofacial defect. The best candidate for the putative target gene is LHX8, located 49 149 bp upstream of the deletion. The gene is known to be associated with facial development in several animals. Four other family members had a subclinical phenotype - a simple notch in the lower lip or an increase in the interdental distance between the lower incisors - indicative of very low-level expression of the trait.

• 出版日期2014-3