Pedigree analysis of autosomal recessive hereditary woolly hair caused by LIPH gene mutation
Objective To analyze the clinical data of a family with autosomal recessive hereditary woolly hair and to investigate the features of pathogenicity-related gene mutations.Methods The clinical data of a family with autosomal recessive hereditary woolly hair were collected,the peripheral blood samples of the proband and his parents were collected,the genomic DNA was extracted,and the gene variation in exon coding regions of dermatosis related genes in the proband was detected by high-throughput sequencing.The pathogenicity-related gene mutation was verified by PCR-Sanger sequencing.ClustalX 2.1 software was used to analyze the conservatism of gene mutation sites,and PyMOL software was used to predict the protein structural variation of gene mutation sites.Results The proband was a 7-year-old boy with diffuse hair decrease from the age of 1 year old and gradually lightening in color.After 3 years old,his hair grew slowly.The clinical manifestations at the time of visit included diffuse hair thinning,and fine and curly in light brown color on the scalp;normal skin color and texture of the scalp,normal number and color of eyebrows,eyelashes and body hair,and normal skin sweating;normal toenails,and no abnormalities such as hyperkeratosis of the palmar and plantar skin;defect in maxillary central incisor and left maxillary lateral incisor,and caries in upper right deciduous tooth 1 and upper left deciduous tooth 2.Dermatoscopy showed generally normal skin,sparse hair,a large number of single hair,and no black spot signs,broken hair or exclamation mark shaped hair.Gene sequencing results showed that the LIPH gene of the proband was c.530T＞G(p.Leu177Arg)and c.736T＞A(p.Cys246Ser)complex heterozygous variation,resulting in the change of Leu to Arg at amino acid 177 and Cys to Ser at amino acid 246 in LIPH gene.The proband's mother carried LIPH gene c.736T＞A(p.Cys246Ser)heterozygous mutation,the proband's father carried LIPH gene c.530T＞G(p.Leu177Arg)heterozygous mutation.The LIPH protein encoded by the three species(human,mouse,canine)was highly conserved at amino acids 177 and 246.The mutation sites of LIPH gene corresponding protein structure changed,which might affect protein function.The proband was diagnosed with autosomal recessive hereditary woolly hair caused by LIPH gene mutation on the basis of his clinical manifestations,family genetic characteristics,gene sequencing,and biological information software prediction.Conclusion Complex heterozygous variants in the LIPH genes c.530T＞G(p.Leu177Arg)and c.736T＞A(p.Cys246Ser)are probably the causative agents of autosomal recessive hereditary woolly hair of the family.
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