Department of Dermatology, Peking University People's Hospital, Beijing, China.
Department of Dermatology, Guangdong Provincial people's Hospital, Guangzhou, China.
Mol Genet Genomic Med. 2022 Apr;10(4):e1889. doi: 10.1002/mgg3.1889. Epub 2022 Feb 11.
Monilethrix is a rare hereditary hair loss disorder characterized by hair fragility and beaded hair shaft alterations. Monilethrix is classically inherited in an autosomal dominant (AD) fashion caused by variants in the hair keratin genes KRT81, KRT83, or KRT86. Interestingly, an autosomal recessive (AR) form of monilethrix with variants in DSG4 gene has also been reported in recent years.
To identify causative variants in Chinese patients with autosomal recessive (AR) form of monilethrix.
Three families with AR form of monilethrix were observed and sequence variant analysis of DSG4 was performed by polymerase chain reaction (PCR), quantitative real-time PCR, and DNA sequencing.
All the patients had sparse, fragile hair involving the scalp, eyebrows, and eyelashes with keratotic follicular papules and pruritus since birth. Atypical-beaded hairs and broken hair shaft fragments were identified in all the patients under dermoscopy. Heterozygous variants c.837del and c. 2389C > T, a homozygous splice site variant c.2355 + 1G > A, and a homozygous 48,644 bp large deletion variant g.31381440_31430084del in the DSG4 gene were identified and verified in the families.
This report provided further evidence for the phenotypic spectrum and clinical features of, and the expanded variant database of AR form of monilethrix.
多发性毳毛症是一种罕见的遗传性毛发缺失疾病，其特征为毛发脆弱和串珠样毛发改变。多发性毳毛症经典的遗传方式为常染色体显性遗传（AD），由头发角蛋白基因 KRT81、KRT83 或 KRT86 的变异引起。有趣的是，近年来也有报道称，常染色体隐性遗传（AR）形式的多发性毳毛症与 DSG4 基因的变异有关。
鉴定中国 AR 形式多发性毳毛症患者的致病变异。
观察三个 AR 形式多发性毳毛症家系，通过聚合酶链反应（PCR）、实时定量 PCR 和 DNA 测序对 DSG4 进行序列变异分析。
所有患者均自出生起出现头皮、眉毛和睫毛稀疏、脆弱的毛发，伴有角化滤泡丘疹和瘙痒。所有患者的皮肤镜下均可见非典型串珠样毛发和断裂的毛发片段。在三个家系中鉴定并验证了 DSG4 基因的杂合变异 c.837del 和 c.2389C>T、纯合剪接位点变异 c.2355+1G>A 和纯合 48,644bp 大片段缺失变异 g.31381440_31430084del。
本报告进一步证实了 AR 形式多发性毳毛症的表型谱、临床特征及扩展的变异数据库。
