Mutation Analysis Of LSS Gene In A Patient With Congenital Hypotrichosis And Her Family

Objective: To increase awareness of the clinical and genetic feature of congenital hypotrichosis by clinical information,family survey study and the analysis of gene;to discuss the relationship and molecular mechanism between LSS gene mutation and clinical phenotype and pathophysiological changes of patient.Methods: Collected and analyzed the clinical data of the patient;Collected the blood sample of the congenital hypotrichosis family for laboratory tests and whole exome sequencing;Obtained the amino acid sequence of mutated lanosterol synthase from NCBI database,imported the sequence into Swiss-model software and performing homology modeling,and then used Swiss-Pdb Viewer software to predict the three-dimensional structure of the protein;Tissue biopsy of scalp tissue and immunohistochemical staining of CD68,INOS and CD163 were performed to analyze the pathological characteristics and macrophage infiltration of scalp tissues.Results:(1)The patient was a 4-year-old girl with sparse hair for four years.Her parents’ hair was normal.There was no similar patient in the family.The physical examination of this patient showed that the hair was sparse,different thickness and length,soft,yellowish color and scattered on white hair.No obvious abnormality was found in eyelashes,eyebrows and body hair;The teeth,tongue,toenails,eye and sweating were normal.intelligence was normal.Dermoscopy displayed that dense white dot,scattered yellow dots,single hair follicle unit was unevenly distributed,the diameter of the hair shaft became thinner,and pig tail hair and erect regrowth were seen.(2)The whole exome sequenced showed that the LSS gene of the patient was a compound heterozygous mutation of the LSS gene(c.1303C> T and c.1029 del C),where c.1303C> T comes from the father and c.1029 del C comes from the mother,no mutation was found in the LSS gene of her brother.(3)The c.1303C>T mutation results in the deletion of amino acid residues and changes in the hydrogen bonding between the amino acid residues.The c.1029 del C mutation results in the deletion of most amino acid residues.(4)The patient’s peripheral blood cholesterol and sex hormones were normal,cortisol was abnormal,and25-hydroxy vitamin D3 decreased.(5)The histopathology displayed mostly that the density of hair follicles in the dermis was reduced,the diameter and length were reduced,and the hair were transformed into small terminal hairs and vellus hairs.Immunohistochemical staining revealed positive expression of CD68,i NOS and CD163 in the inflammatory cells around some hair follicles.Conclusion:(1)The patient was diagnosis as autosomal recessive hypotrichosis simplex and the LSS gene of the patient is a compound heterozygous mutant(c.1303C> T and c.1029 del C).(2)LSS gene mutations do not necessarily cause abnormalities of cholesterol and its metabolites in peripheral blood.(3)The pathological changes of scalp tissue in the patients with LSS gene associated with congenital hypotrichosis is similar to other types of congenital hypotrichosis.Whether macrophage infiltration around the hair follicle is related to the occurrence of congenital hypotrichosis needs to be confirmed by further studies.