Abstract
Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, 10 genes have been identified to be causative for ARCI. NIPAL4 (Nipa-Like Domain-Containing 4) is the second most commonly mutated gene in ARCI. In this study, we present a large cohort of 101 families affected with ARCI carrying mutations in NIPAL4. We identified 16 novel mutations and increase the total number of pathogenic mutations in NIPAL4 to 34. Ultrastructural analysis of biopsies from six patients showed morphological abnormalities consistent with an ARCI EM type III. One patient with a homozygous splice site mutation, which leads to a loss of NIPAL4 mRNA, showed additional ultrastructural aberrations together with a more severe clinical phenotype. Our study gives insights into the frequency of mutations, a potential hot spot for mutations, and genotype-phenotype correlations.
Highlights
Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of rare genetic skin disorders and is characterized by abnormal scaling of the skin over the whole body (Fischer, 2009)
We present a large cohort of 101 families affected with ARCI carrying mutations in Nipa‐Like Domain‐Containing 4 (NIPAL4)
Patients with ARCI from 101 families carrying mutations in NIPAL4 were identified by Sanger sequencing or by ‐generation sequencing methods (Table 1)
Summary
Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of rare genetic skin disorders and is characterized by abnormal scaling of the skin over the whole body (Fischer, 2009). Since its first identification by Lefèvre et al, in 2004, 18 disease‐causing mutations have been reported in NIPAL4 including the highly recurrent mutation c.527C>A, p.(Ala176Asp; Balci et al, 2017; Bučková et al, 2016; Dahlqvist et al, 2007; Kusakabe et al, 2017; Lefèvre et al, 2004; Maier, Mazereeuw‐Hautier, Tilinca, Cosgarea, & Jonca, 2016; Palamar et al, 2015; Scott et al, 2013; Wajid, Kurban, Shimomura, & Christiano, 2010) Clinical phenotypes in this molecular genetically characterized subgroup of ARCI are heterogeneous and show interfamilial, intrafamilial, and intraindividual variability (Alavi et al, 2012; Vahlquist et al, 2018). In both LI and CIE, the presence or absence of a collodion membrane at birth, ectropion and anhidrosis have been reported in patients with mutations in NIPAL4 (Alavi et al, 2012; Dahlqvist et al, 2007; Lefèvre et al, 2004)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
