A case of Carvajal syndrome caused by a spontaneous mutation in the desmoplakin gene / 中华皮肤科杂志

Objective@#To report a case of Carvajai syndrome caused by a spontaneous mutation in the desmoplakin (DSP) gene.@*Methods@#Clinical data were collected form a patient with Carvajal syndrome in Department of Dermatology, The First Affiliated Hospital of Zhengzhou University. Peripheral blood samples were obtained from the proband, his parents and 100 unrelated healthy controls, and blood genomic DNA was extracted. The ion torrent PGM second-generation sequencing platform was used to detect sequence variations in coding regions of exons in skin disease-related genes in the proband and his parents, and the pathogenic variation was verified by PCR-Sanger sequencing.@*Results@#The proband clinically presented with woolly hair, diffuse palmoplantar keratoderma, onychodysplasia, hypodontia and sinus arrhythmia as shown by electrocardiogram. Gene sequencing revealed a heterozygous missense mutation c.1790C>T (p.Ser597Leu) in exon 14 of the DSP gene in the proband, resulting in the substitution of serine by leucine at amino acid position 597. No mutation was identified in the proband′s parents or the 100 healthy controls, so the mutation in the proband is spontaneous. The patient was finally diagnosed with Carvajal syndrome according to the clinical manifestations, gene detection and auxiliary examination results.@*Conclusion@#The heterozygous missense mutation C.1790C>T (p.Ser597Leu) of the DSP gene may be the pathogenic mutation for the clinical phenotype of the patient.

Desmoglein 4 gene mutation analysis in a pedigree with autosomal recessive hereditary monilethrix / 中华皮肤科杂志

A 3-year-old female proband presented with patchy follicular keratotic papules on the hairless scalp after birth. At about the age of 2 years, sparse hairs of non-uniform thickness began to grow, but they fell out intermittently and were broken easily. Some eyebrows and eyelashes of different lengths fell out or were broken. Physical examination revealed good condition of nutrition, normal height, weight and intelligence, with no obvious abnormalities in other systems. Skin examination showed sparse and broken hairs with follicular keratotic papules on the vertex and occiput. Teeth, nails, toenails and sweat glands were normal. Dermoscopy, optical microscopy and scanning electron microscopy all showed that affected hairs gave a beaded appearance. Gene sequencing showed that the proband carried heterozygous deletions of exons 2-16 in the desmoglein 4 (DSG4) gene, and a heterozygous mutation c.574T>C (p.S192p) (NM-177986) in the DSG4 gene, which were inherited from her father and mother respectively. None of the above mutations in the DSG4 gene were found in 100 healthy controls. According to the gene sequencing results and clinical phenotype, the patient was finally diagnosed with autosomal recessive hereditary monilethrix, and the c.574T>C mutation and heterozygous deletions of exons 2-16 of the DSG4 gene may contribute to autosomal recessive hereditary monilethrix in the child.

Desmoglein 4 gene mutation analysis in a pedigree with autosomal recessive hereditary monilethrix / 中华皮肤科杂志

A 3-year-old female proband presented with patchy follicular keratotic papules on the hairless scalp after birth.At about the age of 2 years,sparse hairs of non-uniform thickness began to grow,but they fell out intermittently and were broken easily.Some eyebrows and eyelashes of different lengths fell out or were broken.Physical examination revealed good condition of nutrition,normal height,weight and intelligence,with no obvious abnormalities in other systems.Skin examination showed sparse and broken hairs with follicular keratotic papules on the vertex and occiput.Teeth,nails,toenails and sweat glands were normal.Dermoscopy,optical microscopy and scanning electron microscopy all showed that affected hairs gave a beaded appearance.Gene sequencing showed that the proband carried heterozygous deletions of exons 2-16 in the desmoglein 4 (DSG4) gene,and a heterozygous mutation c.574T＞C(p.S192p)(NM-177986) in the DSG4 gene,which were inherited from her father and mother respectively.None of theabove mutations in the DSG4 gene were found in 100 healthy controls.According to the gene sequencing results and clinical phenotype,the patient was finally diagnosed with autosomal recessive hereditary monilethrix,and the c.574T ＞ C mutation and heterozygous deletions of exons 2-16 of the DSG4 gene may contribute to autosomal recessive hereditary monilethrix in the child.