Netherton Syndrome: Disease Expression and Spectrum of SPINK5 Mutations in 21 Families

A synonymous mutation in SPINK5 exon 11 causes Netherton syndrome by altering exonic splicing regulatory elements

“…Sequence analysis of the entire gene showed that the affected patient was compound heterozygote for the recurrent frameshift mutation c.153delT 7 in exon 3 of the paternal allele and for the novel variant c.891C4T in exon 11 of the maternal allele ( Figure 1c). The patient was also heterozygous for the frequent SNP c.1004C/T in exon 11 (rs34482796, minor allele frequency: T¼0.41).…”

“…3,4 Differentiated keratinocytes synthesize three different LEKTI precursors, which are rapidly processed and then secreted into several shorter bioactive fragments. 5,6 The SPINK5 mutation database in NS comprises 62 different mutations, [7][8][9][10] and the genotype-phenotype correlation suggests that downstream mutations may partly allow for residual expression of functional LEKTI fragments, which results in less severe phenotypes. 11,12 Here we report on functional characterization of the c.891C4T variant identified in the SPINK5 gene in an Italian patient with NS.…”

L’élastase 2, une nouvelle protéase épidermique impliquée dans l’établissement de la barrière cutanée

“…La triade clinique classique du SN comprend : (1) une érythrodermie desquamative congénitale, qui associe une rougeur intense et une exfoliation marquée de la couche superficielle de l'épiderme, (2) une dysplasie pilaire spécifique appelée Trichorrhexis invaginata ou cheveu bambou et (3) des manifestations atopiques constantes et sévères comprenant des L'exfoliation des cornéocytes à la surface de l'épiderme, appelée desquamation, implique la dégradation progressive de la desmogléine-1, la desmocolline-1 et la cornéodesmosine, protéines constitutives des jonctions intercellulaires des cornéocytes, les cornéodesmosomes. Ce processus est rendu possible par l'action de protéases spécifiques comme des protéases à sérine ( [18]. Dans l'épiderme, LEKTI est spécifiquement exprimé dans la couche granuleuse où se déroulent des étapes cruciales pour l'élaboration de la barrière cutanée [19].…”

Prenatal diagnosis of Comel-Netherton syndrome with PGD, case report and review article

“…The hallmark of C-NS is trichorrhexis invaginata (bamboo hair), but other abnormalities, including pili torti (twisted hair) and trichorrhexis nodosa (hair of varying diameter) have been observed. Markedly elevated IgE levels, allergic reactions to food and common antigens, malnutrition, and increased susceptibility to skin, respiratory tract or systemic infections are also characteristic [6,7].…”

“…There are nearly 150-160 cases of C-NS reported in the literature, its incidence might be 1/200.000 [6] due to challenging diagnostic problems during infancy and early childhood. This syndrome has overlapping features with atopic dermatitis and other recessive ichthyosis.…”