Midiutaton Stuy Of Pathogenc Gene In Cases With Marie Unna Hereditary Hypotrichosis

Background Marie Unna Hereditary Hypotrichosis （MUHH, OMIM146550/612841）is a genetic heterogeneity genodermatosis, which is a rare autosomal dominant,inheritance disorder. This disease was firstly described in1925by the Germandermatologist Marie Unna. It is characterized by normal, sparse or absent hair at birth,then developed to coarse, wiry, twisted hair during childhood and was followed by thedevelopment of alopecia in the second or third decade. But no other ectodermalabnormalities are observed.So far, two loci for this disorder have been mapped tochromosome8p21.3and1p21.1-q21.3. In2009, Wen etal identified heterozygosity for aninitiation codon mutation in an ORF （which they designated U2HR） in the5-prime UTRof the HR gene and established a mutation spectrum through international cooperation in19different ethic families with a confirmed clinical diagnosis of MUHH. Functionalanalysis showed that these mutations all increased translation of the main HR physiologicORF and these fine tuning of HR protein levels is important in control of hair growth.Followed then multiple research groups identified the pathogenic mutation of U2HR.Recently, Zhang Xin et al identified a pathogenic missense mutation in EPS8L3（NM₀24526.3） within1p21.1-1q21.3, which suggested that EPS8L3is another causativegene for MUHH.Objective To search for the mutations of U2HR and EPS8L3gene in a Chinese Hanpedigree and a sporadic case with MUHH, then sum up the correlation of clinicalphenotype and genotype in MUHH. Method （1） We analysis the clinical features of MUHH though pedigree investigationand scanning electron microscopy examination.（2） Respectively by PCR reactionamplification of all exons of U2HR area and EPS8L3gene coding region and intronssplice sites, using direct sequencing method for MUHH patients U2HR and EPS8L3genemutation detection.（3） Genotype-phenotype correlation analysisResults There is no mutation in U2HR and EPS8L3gene in the sporadic case throughdirect sequencing. We found a novel heterozygous nonsense mutation C.25C>T（p.Q9X）in our Chinese family with MUHH. But this mutation was absent from unaffectedindividual of the family in addition to200healthy controls. There is no significantcorrelation between genotype and phenotype.Conclusions （1） We provided a distinct MUHH case associated with many otherabnormalities.（2） Identified a novel nonsense mutation of U2HR gene in other case.（3）These findings contribute to better understanding of clinical phenotype and molecularpathogenesis of MUHH.