Clinical and genetic investigation of ichthyosis in familial and sporadic cases in south of Tunisia: genotype-phenotype correlation

BMC Med Genomics. 2022 Jan 5;15(1):4. doi: 10.1186/s12920-021-01154-z.


Background: Ichthyosis is a heterogeneous group of Mendelian cornification disorders that includes syndromic and non-syndromic forms. Autosomal Recessive Congenital Ichthyosis (ARCI) and Ichthyosis Linearis Circumflexa (ILC) belong to non-syndromic forms. Syndromic ichthyosis is rather a large group of heterogeneous diseases. Overlapping phenotypes and genotypes between these disorders is a major characteristic. Therefore, determining the specific genetic background for each form would be necessary.

Methods: A total of 11 Tunisian patients with non-syndromic (8 with ARCI and 2 with ILC) and autosomal syndromic ichthyosis (1 patient) were screened by a custom Agilent HaloPlex multi-gene panel and the segregation of causative mutations were analyzed in available family members.

Results: Clinical and molecular characterization, leading to genotype-phenotype correlation in 11 Tunisian patients was carried out. Overall, we identified 8 mutations in 5 genes. Thus, in patients with ARCI, we identified a novel (c.118T > C in NIPAL4) and 4 already reported mutations (c.534A > C in NIPAL4; c.788G > A and c.1042C > T in TGM1 and c.844C > T in CYP4F22). Yellowish severe keratoderma was found to be associated with NIPAL4 variations and brachydactyly to TGM1 mutations. Two novel variations (c.5898G > C and c.2855A > G in ABCA12) seemed to be features of ILC. Delexon13 in CERS3 was reported in a patient with syndromic ichthyosis.

Conclusions: Our study further extends the spectrum of mutations involved in ichthyosis as well as clinical features that could help directing genetic investigation.

Keywords: ABCA12; CERS3; CYP4F22; Ichthyosis; NIPAL4; TGM1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Association Studies
  • Humans
  • Ichthyosiform Erythroderma, Congenital* / genetics
  • Ichthyosis* / genetics
  • Mutation
  • Phenotype
  • Tunisia