Sixteen novel mutations in <i>PNPLA1</i>
 in patients with autosomal recessive congenital ichthyosis reveal the importance of an extended patatin domain in <i>PNPLA1</i>
 that is essential for proper human skin barrier function

Zimmer, Andreas; Kim, G.J.; Hotz, Alrun; Bourrat, E.; Haußer, Ingrid; Has, Cristina; Oji, Vinzenz; Stieler, Karola; Vahlquist, Anders; Kunde, V.; Weber, Benedikt; Radner, Franz P.W.; Leclerc‐Mercier, Stéphanie; Schlipf, Nina; Demmer, Philipp; Küsel, J.; Fischer, Judith

doi:10.1111/bjd.15308

Cited by 28 publications

(33 citation statements)

References 21 publications

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“…In this issue of the BJD , Zimmer et al . report 16 novel mutations in PNPLA1 in patients with ARCI as a result of screening > 700 families with ichthyosis, thus suggesting that the frequency of PNPLA1 mutations among all patients with ARCI is around 3% . These findings complement a recent publication which also reported six novel mutations in PNPLA1 in nine extended consanguineous families in a cohort of 92 families .…”

supporting

confidence: 79%

Expanding mutation landscape and phenotypic spectrum of autosomal recessive congenital ichthyosis

2017

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supporting

confidence: 79%

Expanding mutation landscape and phenotypic spectrum of autosomal recessive congenital ichthyosis

2017

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“…[21][22][23] To date, 26 different PNPLA1 mutations have been reported associated with ARCI. 17,[24][25][26][27]30 In the present study, we report two novel mutations, including one missense mutation c.335C>A (p.Ser112Tyr) and one deletion mutation c.733_735delTAC (p.Tyr245del), and also one previously reported missense mutation c.514G>A (p.Asp172Asn) in PNPLA1 gene in seven ARCI patients from three consanguineous Turkish families.…”

supporting

confidence: 56%

“…Clinical findings of our ARCI patients were commonly similar to previously reported symptoms. 25 Generally, the symptoms of ARCI patients with PNPLA1 mutations are relatively milder than the other forms of ARCI especially caused by TGM1 and ABCA12 mutations. 25 ARCI causing genes play important roles in differentiation of epidermal keratinocytes and/or formation of epidermal lipid barrier.…”

Section: Discussionmentioning

confidence: 98%

Identification of two novel PNPLA1 mutations in Turkish families with autosomal recessive congenital ichthyosis

et al. 2017

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Dökmeci-Emre S, Taşkıran ZE, Yüzbaşıoğlu A, Önal G, Akarsu AN, Karaduman A, Özgüç M. Identification of two novel PNPLA1 mutations in Turkish families with autosomal recessive congenital ichthyosis. Turk J Pediatr 2017; 59: 475-482. Autosomal recessive congenital ichthyosis (ARCI) is a group of inherited keratinization disorders that are characterized by abnormal epidermal keratinization. ARCI patients generally represent serious symptoms including collodion baby phenotype accompanied by dehydration, heat loss, electrolytic imbalance, and sepsis. ARCI shows high degree of clinical and genetic heterogeneity. To date, nine genes were shown to be responsible for ARCI phenotype. One of these genes, patatin-like phospholipase domain containing protein-1 (PNPLA1) was suggested to be involved in the synthesis of ω-O-acylceramides related to epidermal cornified lipid envelope organization. In addition to previously reported PNPLA1 mutations, we report two novel PNPLA1 mutations including one novel missense mutation c.335C > A (p.Ser112Tyr) and one novel deletion mutation c.733_735delTAC (p.Tyr245del) in Turkish ARCI patients from unrelated consanguineous families. We also report previously reported missense mutation c.514G > A (p.Asp172Asn) in Turkish ARCI patients. Novel PNPLA1 mutations were shown to be located in the catalytic patatin domain of PNPLA1 gene. Identification of novel mutations in PNPLA1 gene expands the mutational spectrum in the causative gene. Increase in the total number of cases has high diagnostic value in terms of genotype-phenotype correlation in ARCI patients.

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“…In some populations, PNPLA1 and CERS3 mutations are very rare, while in our Iranian cohort, PNPLA1 was the second most common mutated gene accounting for 19 of the 125 ARCI families (15.2%). Additional families with PNPLA1 mutations have also recently been reported, attesting to the increasing recognition of the prevalence of mutations in this gene (Boyden et al., ; Zimmer et al., ). A unique aspect of our cohort is that 90% of cases come from consanguineous families, as evidenced by the fact that 102 of the 106 cases (96.2%) with pathogenic mutations were homozygous for the variant.…”

Section: Discussionmentioning

confidence: 96%

Autosomal recessive congenital ichthyosis: Genomic landscape and phenotypic spectrum in a cohort of 125 consanguineous families

et al. 2019

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Autosomal recessive congenital ichthyosis (ARCI), a phenotypically heterogeneous group of non‐syndromic Mendelian disorders of keratinization, is caused by mutations in as many as 13 distinct genes. We examined a cohort of 125 consanguineous families with ARCI for underlying genetic mutations. The patients’ DNA was analyzed with a gene‐targeted next generation sequencing panel comprising 38 ichthyosis associated genes. The interpretations of results of genomic data were assisted by genome‐wide homozygosity mapping and transcriptome sequencing. Sequence data analysis identified biallelic mutations in 106 families out of a total of 125 (85%), most of them (102, 96.2%) being homozygous, reflecting consanguinity in these families. Among the 85 distinct mutations in 10 different genes, 45 (53%) were previously unreported. Phenotype‐genotype correlations allowed assignment of specific genes in the majority of the families to a specific subtype of ARCI, lamellar ichthyosis (LI) versus congenital ichthyosiform erythroderma (CIE). Interestingly, mutations in several genes could give rise to an overlapping phenotype consistent with either LI or CIE. Also, this is the third report for SDR9C7 and SULT2B1, and fourth report for CERS3 mutations. Direct comparison of our results with previously published regional cohorts highlights the global mutation landscape of ARCI, however, population specific differences were noted.

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Sixteen novel mutations in PNPLA1 in patients with autosomal recessive congenital ichthyosis reveal the importance of an extended patatin domain in PNPLA1 that is essential for proper human skin barrier function

Cited by 28 publications

References 21 publications

Expanding mutation landscape and phenotypic spectrum of autosomal recessive congenital ichthyosis

Expanding mutation landscape and phenotypic spectrum of autosomal recessive congenital ichthyosis

Identification of two novel PNPLA1 mutations in Turkish families with autosomal recessive congenital ichthyosis

Autosomal recessive congenital ichthyosis: Genomic landscape and phenotypic spectrum in a cohort of 125 consanguineous families

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