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

Abstract 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.

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Variants in the PNPLA1 Gene in Families with Autosomal Recessive Congenital Ichthyosis Reveal Clinical Significance

Molecular Syndromology ◽

10.1159/000516943 ◽

2021 ◽

pp. 1-11

Author(s):

Farooq Ahmad ◽

Ishtiaq Ahmed ◽

Qamre Alam ◽

Tanveer Ahmad ◽

Ammara Khan ◽

...

Keyword(s):

Sanger Sequencing ◽

Autosomal Recessive ◽

Genetic Disorders ◽

Genetic Diagnosis ◽

Missense Variant ◽

Sequence Variant ◽

Phenotype Correlation ◽

Congenital Ichthyosis ◽

Whole Exome ◽

Autosomal Recessive Congenital Ichthyosis

The term autosomal recessive congenital ichthyosis (ARCI) is the subgroup of ichthyosis, which describes a highly heterogeneous group of genetic disorders of the skin characterized by cornification and defective keratinocytes differentiation associated with mutations in at least 14 genes including PNPLA1. To study the molecular basis of the Pakistani kindreds (A and B) affected by ARCI, whole-exome sequencing (WES) in the DNA samples of affected members was performed followed by Sanger sequencing of the candidate gene to hunt down the disease-causing sequence variant/s. WES data analysis led to the identification of a novel nonsense sequence variant (c.892C>T; p.Arg298*, family A) and a recurrent missense variant (c.102C>A; p.Asp34Glu, family B) in PNPLA1 mapped to the ARCI locus in chromosome 6p21.31. Validation and cosegregation analysis of the variants in the remaining family members of the respective families were confirmed by Sanger sequencing. The current investigation expands the spectrum of PNPLA1 mutations and helps establish the proper clinico-genetic diagnosis and correct genotype-phenotype correlation.

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Transglutaminase 1 deficiency and corneocyte collapse: an indication for targeted molecular screening in autosomal recessive congenital ichthyosis

British Journal of Dermatology ◽

10.1111/j.1365-2133.2007.08070.x ◽

2007 ◽

Vol 157 (4) ◽

pp. 808-810 ◽

Cited By ~ 10

Author(s):

G. Esposito ◽

G. Tadini ◽

F. Paparo ◽

A. Viola ◽

L. Ieno ◽

...

Keyword(s):

Autosomal Recessive ◽

Molecular Screening ◽

Congenital Ichthyosis ◽

Transglutaminase 1 ◽

Autosomal Recessive Congenital Ichthyosis

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ABCA12 mutations and autosomal recessive congenital ichthyosis: A review of genotype/phenotype correlations and of pathogenetic conceptsa

Human Mutation ◽

10.1002/humu.21326 ◽

2010 ◽

Vol 31 (10) ◽

pp. 1090-1096 ◽

Cited By ~ 64

Author(s):

Masashi Akiyama

Keyword(s):

Autosomal Recessive ◽

Congenital Ichthyosis ◽

Autosomal Recessive Congenital Ichthyosis

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Mutations in Transglutaminase 1 Gene in Autosomal Recessive Congenital Ichthyosis in Egyptian Families

Disease Markers ◽

10.1155/2004/965968 ◽

2004 ◽

Vol 20 (6) ◽

pp. 325-332 ◽

Cited By ~ 8

Author(s):

R. M. Shawky ◽

N.S. Sayed ◽

N.A. Elhawary

Keyword(s):

Restriction Endonuclease ◽

Splice Site ◽

Autosomal Recessive ◽

Splice Mutation ◽

The Other ◽

Splice Acceptor ◽

Acceptor Splice Site ◽

Congenital Ichthyosis ◽

Transglutaminase 1 ◽

Autosomal Recessive Congenital Ichthyosis

Autosomal recessive congenital ichthyosis (ARCI) is a rare heterogeneous keratinization disorder of the skin. It is clinically divided into 2 subtypes, lamellar ichthyosis (LI) and congenital ichthyosiformis erythroderma (CIE). We investigated forty-three ARCI Egyptian individuals in 16 severe LI, and 10 CIE families. We identified 5 alleles in two Egyptian families as having intron-5/exon-6 splice acceptor mutation recognized by theMspIrestriction endonuclease. This promoted to a frequency of 9.6% for this mutation (5 splice-mutation alleles/52 alleles tested). We extended our previous dataset to update the detection of R142H mutation in 4 CIE Egyptian families and one LI phenotype (frequency of 28.8%; 15/52), whereas we still had no R141H among our Egyptian population. There was no correlation between phenotype and genotype in our study. Surprisingly, the mutant alleles detected in intron-5 acceptor splice-site were associated with the other extreme of CIE phenotypes rather than the severe LI form. We clearly demonstrated that the ARCI Egyptian families in Upper Egypt was ethnically pure and had a tendency not to be a hybrid with other populations in Lower Egypt, Delta zone and Cairo city.

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