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. 2025 Jul 25;105:41100. doi: 10.2340/actadv.v105.41100

The Clinical Spectrum of Rare Inherited Ichthyosis in China: A Review of Thirty-five Cases

Ruiyu XIANG 1,#, Xin HUANG 1,#, Yihe LIU 1, Shuya SUN 1, Di HUA 1, Ran MO 1, Yong YANG 1, Zhiming CHEN 1,*
PMCID: PMC12308539  PMID: 40709761

Abstract

Inherited ichthyosis comprises a spectrum of genetic disorders related to over 50 pathogenic genes. However, there are limited data summarizing the clinical and molecular characteristics of Chinese patients. To broaden the knowledge of clinical and genetic characteristics of inherited ichthyosis and to optimize disease diagnosis and therapies, cases diagnosed with inherited ichthyosis in 1 tertiary centre from 2019 to 2023 were collected, excluding ichthyosis vulgaris and X-linked recessive ichthyosis, genomic sequencing was then performed, and clinical details of the patients were assessed. A total of 35 patients from Jiangsu and Anhui provinces of China were enrolled, 31 of whom were diagnosed with non-syndromic ichthyosis. Within this group, there were cases of autosomal recessive congenital ichthyosis (18/31), epidermolytic ichthyosis (9/31), and superficial epidermolytic ichthyosis (4/31). Additionally, 4 patients were diagnosed with syndromic ichthyosis, comprising 1 case of Chanarin–Dorfman syndrome and 3 cases of Netherton syndrome. The genetic analysis revealed a total of 47 variants across 13 genes, of which 19 were identified as novel variants. This study describes the clinical spectrum of rare inherited ichthyosis in the Jiangsu-Anhui region of China and further expands the genetic characteristics of the disease.

Key words: congenital ichthyosiform erythroderma, epidermolytic ichthyosis, ichthyosis, Netherton syndrome

SIGNIFICANCE

Inherited ichthyosis is a group of rare inherited skin disorders with multiple types. Among them, ichthyosis vulgaris and X-linked recessive ichthyosis have a high prevalence and are relatively easy to diagnose, while the diagnosis of rare ichthyoses remains challenging. This study enrolled 35 cases with rare ichthyosis and analysed their clinical and genetic characteristics and heterogeneity. Our genetic analysis revealed a total of 47 variants across 13 genes, of which 19 new variants are first reported here. Thus, this work further expands the clinical and genetic spectrum of ichthyosis and provides more information for dermatologists to help diagnose rare ichthyosis.

Inherited ichthyosis constitutes a group of genodermatoses characterized by widespread dry skin, scaling, and hyperkeratosis. Clinical manifestations may extend to abnormalities in skin appendages and other organ systems (1). Timely diagnosis of inherited ichthyosis is imperative due to the diverse prognoses associated with different subtypes. Ichthyosis vulgaris (2) and X-linked ichthyosis (3) are the most common subtypes of ichthyosis. However, it is challenging to diagnose numerous rare inherited ichthyoses primarily based on clinical features (4). In recent years, advancements in genetic testing technology have helped to identify over 50 genes causing inherited ichthyosis (5). Identifying the genotype of inherited ichthyosis is crucial for advancing clinicians’ comprehension of the condition, facilitating early diagnosis, and enabling effective intervention for associated complications. Furthermore, it can offer evidence-based recommendations for the daily management of patients with inherited ichthyosis (6, 7).

To enhance our understanding of the genomic characteristics of inherited ichthyosis, we conducted an analysis of 35 patients diagnosed with inherited ichthyosis from Jiangsu and Anhui provinces of China, excluding ichthyosis vulgaris and X-linked ichthyosis. Our study expanded the spectrum of pathogenic variants associated with inherited ichthyosis in this distinct region.

MATERIALS AND METHODS

Subjects

From October 2019 to October 2023, we enrolled 35 clinically diagnosed patients with various inherited ichthyosis subtypes (excluding ichthyosis vulgaris and X-linked recessive ichthyosis), recruited from the Genetic Skin Disease Center, Institute of Dermatology, Chinese Academy of Medical Sciences, and Peking Union Medical College. These individuals mainly originated from the Jiangsu–Anhui region in China.

Ethics

The research was approved by the Ethics Committee of the Institute of Dermatology of the Chinese Academy of Medical Sciences and Peking Union Medical College (2019-Clinic-005). The study adhered to the principles and guidelines in the Declaration of Helsinki.

Sample preparation, DNA sequencing, and bioinformatics analyses

Blood samples were collected from all patients and DNA extraction was carried out using a Genomic DNA Kit (Tsingke, Beijing, China). Sanger sequencing was employed for DNA samples from 5 patients (P21, P23, P29, P30, P33), while whole-exome sequencing was performed on DNA samples from an additional 5 patients (P4, P9, P17, P18, P33). The remaining 25 patients underwent testing using a skin next-generation sequencing (NGS) panel comprising 723 target genes (MyGenostics, Beijing, China) (8). Candidate variants identified through next-generation sequencing and family segregation were subsequently validated using Sanger sequencing. Pathogenic variants were determined using pathogenicity prediction tools including REVEL, SIFT, PolyPhen-2, GERP++, and MutationTaster (9).

RESULTS

In our clinic, a comprehensive cohort of 35 patients was evaluated by the same experienced dermatologist. The group comprised 17 males and 18 females, spanning ages from 1 month to 43 years, with 18 individuals below 18 years old. All patients belonged to the Han ethnicity. Genetic testing was performed for all 35 patients, and family members of 19 patients underwent subsequent verification. Initial diagnoses before genetic testing were diverse: 15 patients were diagnosed with congenital ichthyosiform erythroderma (CIE), 3 with lamellar ichthyosis (LI), 9 with epidermolytic ichthyosis (EI), 3 with superficial epidermolytic ichthyosis (SEI), 3 with erythrokeratodermia variabilis (EKV), and 2 with Netherton syndrome. Ultimately, a definitive genetic diagnosis was established for all cases, encompassing 19 novel variants and 10 variants previously reported by our team. Additionally, diagnoses included 18 patients with autosomal recessive congenital ichthyosis (ARCI), 9 with epidermolytic ichthyosis (EI), 4 with SEI, 3 with Netherton syndrome, and 1 with Chanarin–Dorfman syndrome. Detailed patient characteristics and molecular data are summarized in Table I.

Table I.

Clinical and molecular findings in 35 patients with inherited ichthyosis.

Patient code Gender Age Clinical diagnosis Final diagnosis Gene Inheritance Exon Zygosity Mutations (cDNA level) Mutations (protein level) Type ACMG
1 M 22m CIE ARCI ALOX12B AR exon4 Compound heterozygous c.488delGa p.R163Pfs*34 Deletion Likely pathogenic
exon14 c.1876T>Ca p.C626R Missense Uncertain
2 M 3 y LI ARCI ALOX12B AR exon10 Compound heterozygous c.1317C>Aa p.S439R Missense Uncertain
exon10 c.1350dup p.L451Afs*27 Insertion Pathogenic
3 F 10 y CIE ARCI ALOX12B AR exon13 Compound heterozygous c.1694G>C p.R565P Missense Likely pathogenic
exon11 c.1496G>A p.R499H Missense Uncertain
4 F 6 y LI ARCI NIPAL4 AR exon3 Compound heterozygous c.500G>Ca p.W167S Missense Uncertain
exon4 c.741delCa p.T248Pfs*138 Deletion Uncertain
138
5 F 21 y CIE ARCI CERS3 AR exon12 Compound heterozygous exon12 deletionb / Deletion Likely pathogenic
exon11 c.746A>Gb p.K249R Missense Uncertain
6 F 30 y EKV ARCI PNPLA1 AR exon6 Homozygous c.1300delGb p.A434Hfs*22 Deletion Pathogenic
7 M 5 y EKV ARCI PANLA1 AR exon1 Compound heterozygous c.100G>A p.A34T Missense Pathogenic
exon3-8 exon3-8 deletiona / Deletion Likely pathogenic
8 F 7 m CIE ARCI PNPLA1 AR exon2 Compound heterozygous c.434T>Cb p.I145T Missense Likely pathogenic
exon2 c.320T>Ab p.V107D Missense Uncertain
9 F 16m CIE ARCI PNPLA1 AR exon2 Compound heterozygous c.377G>Ab p.R126H Missense Uncertain
exon1 c.100G>Ab p.A34T Missense Likely pathogenic
10 M 29 y CIE ARCI PANLA1 AR exon1 Compound heterozygous c.106C>Ta p.R36W Missense Uncertain
exon1 c.100G>A p.A34T Missense Pathogenic
11 F 23 y LI ARCI SDR9C7 AR exon1 Homozygous c.187C>T p.Q63* Nonsense Pathogenic
12 F 13 y CIE ARCI TGM1 AR exon3 Compound heterozygous c.463C>T p.R155W Missense Likely pathogenic
exon5 c.856C>T p.R286W Missense Pathogenic
13 M 32 m CIE ARCI ABCA12 AR exon51 Compound heterozygous c.7526dela p.P2509Qfs*5 Deletion Likely pathogenic
exon42 c.6233G>Ca p.G2078A Missense Uncertain
14 F 2 y CIE ARCI ABCA12 AR exon27 Compound heterozygous c.3889C>T p.R1297* Missense Pathogenic
intron26 c.3830-5T>Ga / Splicing Uncertain
15 F 20 y CIE ARCI ABCA12 AR exon22 Compound heterozygous c.2984C>Aa p.T995K Missense Uncertain
exon24 c.3304A>Ga p.M1102V Missense Uncertain
16 F 20 y CIE ARCI ABCA12 AR exon2 Homozygous c.130C>T p.R44W Missense Likely pathogenic
17 M 23 y EKV ARCI ABCA12 AR exon49 Compound heterozygous c.7247C>Tb p.P2416L Missense Pathogenic
exon25 c.3653A>Gb p.Y1218C Missense Uncertain
18 F 24 y CIE ARCI ALOXE3 AR exon10 Compound heterozygous c.1235C>A p.T412K Missense Uncertain
exon10 c.1189_1209dupa p.N397_H403dup Insertion Uncertain
up s403dup
s403dup
19 M 3 y EI EI KRT1 AD exon9 Heterozygous c.1617_1618dupTGa p.G540Vfs*75 Insertion Likely pathogenic
20 F 22 y EI EI KRT1 AD exon9 Heterozygous c.1870_1874dela p.K624Lfs*28 Deletion Uncertain
21 M 4 y EI EI KRT10 AD exon7 Heterozygous c.1636dupAa p.S546Kfs*35 Insertion Uncertain
22 F 43 y EI EI KRT10 AD exon1 Heterozygous c.467G>A p.R156H Missense Pathogenic
23 F 5 y EI EI KRT10 AD exon1 Heterozygous c.467G>A p.R156H Missense Pathogenic
24 F 21 y EI EI KRT10 AD exon1 Heterozygous c.466C>T p.R156C Missense Pathogenic
25 F 2 y EI EI KRT10 AD exon6 Heterozygous c.1346A>G p.Y449C Missense Pathogenic
26 M 22 y SEI EI KRT10 AD exon4 Heterozygous c.911_922delTGGA AATGAATGa p.V304_N307del Deletion Uncertain
27 F 6 y EI EI KRT1 AD exon2 Heterozygous c.623T>C p.L208P Missense Pathogenic
28 M 25 y EI SEI KRT2 AD exon7 Heterozygous c.1459G>A p.E487K Missense Pathogenic
29 M 33 y SEI SEI KRT2 AD exon7 Heterozygous c.1459G>A p.E487K Missense Pathogenic
30 M 1 m SEI SEI KRT2 AD exon7 Heterozygous c.1459G>A p.E487K Missense Pathogenic
31 M 30 y CIE SEI KRT2 AD exon7 Heterozygous c.1459G>A p.E487K Missense Pathogenic
32 M 29 y CIE Chanarin–Dorfman syndrome ABHD5 AR exon6 Homozygous c.933dupAb p.R312Tfs*45 Insertion Likely pathogenic
33 M 12 y Netherton syndrome Netherton syndrome SPINK5 AR exon26 Compound heterozygous c.2472_2473delAG p.K824fs*2 Deletion Pathogenic
intron27 c2666+5G>A / Splicing Uncertain
34 M 1 m CIE Netherton syndrome SPINK5 AR exon15 Compound heterozygous c.1303-2A>Ga / Splicing Likely pathogenic
exon24 c.2260A>T p.K754* Nonsense Pathogenic
35 M 33 y Netherton syndrome Netherton syndrome SPINK5 AR exon13 Compound heterozygous c.1111C>T p.R371* Nonsense Pathogenic
exon21 c.2015+1G>Ta / Splicing Pathogenic
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Novel mutations are marked with “a”. Novel mutations reported by our group previously are marked with “b”.

y: years; m: months; CIE: congenital ichthyosiform erythroderma; LI: lamellar ichthyosis; EKV: erythrokeratodermia variabilis; EI: epidermolytic ichthyosis; SEI: superficial epidermolytic ichthyosis; ARCI: autosomal recessive congenital ichthyosis; EI: epidermolytic ichthyosis; AD: autosomal dominant; AR: autosomal recessive.

Autosomal recessive congenital ichthyosis

Among the 18 patients diagnosed with ARCI, various genes were implicated, including ALOX12B (3/18), NIPAL4 (1/18), CERS3(1/18), PNPLA1 (5/18), SDR9C7 (1/18), TGM1(1/18), ABCA12 (5/18), and ALOXE3 (1/18). This involved the identification of 13 novel variants and 9 variants previously reported by our team. For patients P1–P3, presenting with either LI or CIE, variants in the ALOX12B gene were identified. P1 was born with collodion and diagnosed with CIE, carrying a novel deletion mutation c.488delG and a novel missense mutation c.1876T > C. P2, diagnosed with LI, harboured a novel missense mutation c.1317C > A. P4, also diagnosed with LI, had a novel missense mutation c.500G > C and a novel deletion mutation c.741delC in the NIPAL4 gene. Patients P6–P10 harboured variants in the PNPLA1 gene. P6 and P7 (Fig. 1A), initially suspected of EKV due to map-like erythroderma and desquamation with seasonal changes, were ultimately found to have mutations in the PNPLA1 gene. P7 had a novel deletion of exons 3–8. P8–P10 were diagnosed with CIE, including P10 with a novel missense mutation c.106C > T, and P8, who also had a deletion mutation c.3321del in the FLG gene. P11, presenting with LI and onychomycosis, which was confirmed by fungal fluorescent staining (Fig. 1B), had variants in the SDR9C7 gene. P13–P17 had ABCA12 gene variants characterized by at least 1 heterozygous missense mutation. They did not exhibit the characteristic armour-like thick scales encasement, ectropion, and eclabium at birth that is pathognomonic for harlequin ichthyosis (HI), which typically requires biallelic truncating mutations in ABCA12 as established by previous genotype–phenotype correlation studies (10). The observed missense variants in these patients may represent a milder allelic variant of ABCA12-related ichthyosis. P13–P16 displayed CIE, while P17 (11) showed EKV. P13 had a novel deletion mutation c.7526del and a novel missense mutation c.6233G > C. P14 had a novel missense mutation c.3830-5T>G in intron 26 and a missense mutation c.12064A > T in FLG. P15 had novel missense mutations c.2984C>A and c.3304A > G in ABCA12. P18, diagnosed with CIE, had a novel missense mutation c.1317C > A in ALOXE3.

Fig. 1.

Fig. 1

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Clinical photographs of patients with inherited ichthyosis. (A–B) Patients with autosomal recessive congenital ichthyosis. (A) P7, map-like erythroderma and desquamation. (B) P11, lamellar ichthyosis with onychomycosis (37). (C–E) Patients with keratinopathic ichthyosis. (C) P19, hyperkeratosis of the elbow. (D) P24, marble-like hyperkeratosis. (E) P28, collar-like desquamation. (F–G) Patients with Netherton syndrome. (F) P33, ichthyosis linearis circumflexa: erythematous patches with double-edged scales. (G) P34, erythroderma with massive desquamation.

Keratinopathic ichthyosis (KPI)

Among the 13 patients diagnosed with KPI, 3 genes were implicated: KRT1 (3/13), KRT10 (6/13), and KRT2 (4/13), with a total of 4 novel variants identified in this group. P19–P21 exhibited frameshift mutations in either KRT1 or KRT10. P19 presented with dryness of the entire skin and hyperkeratosis in the palmoplantar, knee, groin, and elbow regions (Fig. 1C), carrying a novel insertion mutation c.1617_1618dupTG in KRT1. P20, diagnosed with EI, displayed palmoplantar hyperkeratosis and harboured a novel deletion mutation c.1870_1874del in KRT1. P21, presenting with diffuse erythroderma, desquamation, and itching, was found to have a novel insertion mutation c.1636dupA in KRT10. In other patients with KPI, P24 exhibited marble-like hyperkeratosis in the lower limbs due to inappropriate care, with a mutation in KRT10 (Fig. 1D). P26, initially diagnosed as SEI, had a novel deletion mutation c.911_922delTGGAAATGAATG in KRT10. P28, showing collar-like desquamation in the trunk and upper extremities, was found to have a mutation in KRT2 (Fig. 1E).

Syndromic ichthyosis

In the group of patients with syndromic ichthyosis, 2 genes were implicated: ABHD5 (1/4) and SPINK5 (3/4), revealing 2 novel variants within this subgroup. Patient P32, presenting with mild diffuse erythroderma and desquamation, alongside fatty liver and mild hearing loss, was diagnosed with Chanarin–Dorfman syndrome (12). P33–P35 were diagnosed with Netherton syndrome. P33 displayed classical ichthyosis linearis circumflexa (Fig. 1F). P34, born with extensive desquamation, resembling a collodion baby (Fig. 1G), had a novel missense mutation c.1303-2A>G. A splicing mutation (c.2015+1G>T) was detected in P35.

DISCUSSION

Inherited ichthyosis comprises a group of genetically heterogeneous skin disorders with more than 50 known disease-causing genes. Genetic testing plays a pivotal role in the precise classification of its subtypes. In our cohort of 35 patients, we identified 18 cases of ARCI, 13 of KPI, and 4 of syndromic ichthyosis. The majority of patients underwent next-generation sequencing, followed by Sanger sequencing for validation to minimize the likelihood of missed variants. In five cases with a high degree of clinical certainty, Sanger sequencing only was performed. However, as Sanger sequencing detects only targeted genes, it does not rule out the presence of variants in other pathogenic genes.

Genotypic and phenotypic concordance was observed in most patients. According to ACMG guidelines, the majority of identified variants were classified as “pathogenic”, while a minority were designated as “uncertain” (see Table I). This classification was primarily due to limited supporting evidence, particularly variants meeting only the PM2_Supporting criterion, preventing definitive classification as “pathogenic” or “likely pathogenic”. Nevertheless, our analysis suggests that these variants are likely causative in affected individuals, given the overall genotype–phenotype correlation. ARCI exhibits both genetic and clinical heterogeneity, with biallelic variants identified in at least 13 genes, including TGM1 (13), ABCA12 (14), ALOX12B (15), ALOXE3 (15), CERS3 (16), CYP4F22 (17), LIPN (18), NIPAL4 (19), PNPLA1 (20), SDR9C7 (21), SLC27A4 (22), SULT2B1 (23), and CASP14 (24). The prevalence of pathogenic variants differs geographically. TGM1 and NIPAL4 are more frequently detected in Western populations (6), whereas CYP4F22 and ABCA12 are predominant in the Middle East (25).

In our cohort, we identified 8 disease-associated genes with a total of 31 variants, including 13 variants and 9 previously first reported by our group. PNPLA1(5/17) and ABCA12 (5/17) were the most frequently implicated genes in Chinese patients, though this finding may be influenced by the relatively small sample size and potential ethnic differences. Notably, 2 ARCI patients (P8 and P14) carried a heterozygous variant in the FLG, and the combination of FLG variants was also observed in XLI (26) and ARCI with TGM1 variants (27). Comprehensive analysis revealed that the additional FLG variant did not exacerbate the core ichthyosis phenotype but may have contributed to other dermatological features, such as palmar and plantar hyperlinearity.

Traditionally, ARCI is classified into 3 major subtypes based on clinical presentation: CIE, LI, and HI. However, in our cohort, the phenotypic spectrum of ARCI was better delineated into 3 clinical subtypes: CIE (12/18), LI (3/18), and EKV (3/18). Notably, no patient exhibited HI, likely due to its high neonatal mortality rate and the tendency for such cases to be diagnosed in obstetric and paediatric settings rather than dermatology clinics.

Among the patients, 3 exhibited EKV-like lesions, despite carrying distinct mutations. P6 and P7 harboured PNPLA1 deletion variants and were diagnosed with EKV based on their clinical presentation. P17, another EKV patient, carried compound heterozygous ABCA12 variants, including 1 of uncertain significance (ABCA12: c.3653A>G, p.Y1218C). Notably, none of these patients carried known pathogenic variants in GJB3, GJB4, or GJA1, which are commonly associated with EKV. Detailed physical examinations revealed localized ichthyosis-like features on the extensor surfaces of the limbs and trunk in P6, P7, and P17, supporting their classification as ARCI, complicated by EKV-like features. Previous studies have predominantly linked ABCA12 variants to HI, LI, and CIE, while PNPLA1 variants are commonly associated with CIE (28, 29). Interestingly, recent reports have described similar EKV-like lesions in ARCI patients with ABCA12 (30) and PNPLA1 variants (31). These findings suggest that EKV-like lesions may represent an additional phenotypic manifestation of ARCI, particularly in cases involving disruptions in genes governing lipid metabolism and transport. The observed genetic and clinical heterogeneity underscores the necessity of genetic testing for accurate classification and diagnosis.

Regarding KPI (32–34), 3 patients in our cohort carried novel frameshift variants in KRT1 or KRT10 (35). Notably, none exhibited the characteristic phenotypes of ichthyosis with confetti or ichthyosis hystrix Curth-Macklin, leading to their classification as EI. Long-term clinical follow-up remains crucial for recognizing potential disease progression. While missense variants are typically associated with EI and SEI, P26 presented with only mild desquamation, without overt skin blistering. His KRT10 variant (c.911_922del, p.V304_N307del) is an in-frame deletion located in the linker region of the KRT10 protein, a region not typically associated with keratinopathies, which may explain his mild phenotype and initial misdiagnosis as SEI.

Among the 3 cases of Netherton syndrome (36), 2 harboured novel variants in the intron of SPINK5 resulting in aberrant splicing. Notably, patient P34 exhibited a collodion-like massive desquamation, an atypical presentation for Netherton syndrome.

Our study expands the understanding of the genetic landscape of inherited ichthyosis in the Jiangsu–Anhui region of China and highlights the frequent absence of clear genotype-phenotype correlations. Further studies involving larger cohorts and multicentre collaborations are necessary to refine our understanding of this complex disease spectrum. The widespread application of DNA sequencing has significantly improved the differential diagnosis of ichthyosis. Advances in Sanger sequencing and NGS have deepened our comprehension of the pathophysiology of inherited diseases. In our clinic, genetic testing is guided by clinical presentation, allowing for targeted selection of whole-genome sequencing, whole-exome sequencing, or NGS panel testing, with Sanger sequencing used for validation when necessary. This approach enhances diagnostic efficiency while reducing costs. Molecular diagnosis not only facilitates genetic counselling but also serves as a crucial tool for elucidating disease mechanisms and guiding therapeutic development.

ACKNOWLEDGEMENTS

IRB approval status

The research was approved by the Ethics Committee of the Institute of Dermatology of the Chinese Academy of Medical Sciences and Peking Union Medical College (2019-Clinic-005).

Funding Statement

Funding sources This work was supported by grants from the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-018).

Footnotes

The authors have no conflicts of interest to declare.

REFERENCES

  • 1.Gutiérrez-Cerrajero C, Sprecher E, Paller AS, Akiyama M, Mazereeuw-Hautier J, Hernández-Martín A, et al. Ichthyosis. Nat Rev Dis Primers 2023; 9: 2. 10.1038/s41572-022-00412-3 [DOI] [PubMed] [Google Scholar]
  • 2.Sybert VP, Dale BA, Holbrook KA. Ichthyosis vulgaris: identification of a defect in synthesis of filaggrin correlated with an absence of keratohyaline granules. J Invest Dermatol 1985; 84: 191–194. 10.1111/1523-1747.ep12264813 [DOI] [PubMed] [Google Scholar]
  • 3.Mohandas T, Shapiro LJ, Sparkes RS, Sparkes MC. Regional assignment of the steroid sulfatase-X-linked ichthyosis locus: implications for a noninactivated region on the short arm of human X chromosome. Proc Natl Acad Sci U S A 1979; 76: 5779–5783. 10.1073/pnas.76.11.5779 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Park JS, Saeidian AH, Youssefian L, Kondratuk KE, Pride HB, Vahidnezhad H, et al. Inherited ichthyosis as a paradigm of rare skin disorders: genomic medicine, pathogenesis, and management. J Am Acad Dermatol 2023; 89: 1215–1226. 10.1016/j.jaad.2022.08.012 [DOI] [PubMed] [Google Scholar]
  • 5.Sun Q, Burgren NM, Cheraghlou S, Paller AS, Larralde M, Bercovitch L, et al. The genomic and phenotypic landscape of ichthyosis: an analysis of 1000 kindreds. JAMA Dermatol 2022; 158: 16–25. 10.1001/jamadermatol.2021.4242 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Simpson JK, Martinez-Queipo M, Onoufriadis A, Tso S, Glass E, Liu L, et al. Genotype–phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis. Br J Dermatol 2020; 182: 729–737. 10.1111/bjd.18211 [DOI] [PubMed] [Google Scholar]
  • 7.Cheng R, Liang J, Li Y, Zhang J, Ni C, Yu H, et al. Next-generation sequencing through multi-gene panel testing for diagnosis of hereditary ichthyosis in Chinese. Clin Genet 2020; 97: 770–778. 10.1111/cge.13704 [DOI] [PubMed] [Google Scholar]
  • 8.Liu J, Chen Z, Hu L, Song Z, Mo R, Tsang LS, et al. Investigation of Nagashima-type palmoplantar keratoderma in China: a cross-sectional study of 234 patients. J Dermatol 2023; 50: 375–382. 10.1111/1346-8138.16621 [DOI] [PubMed] [Google Scholar]
  • 9.Liu Y, Tan Y, Liu J, Song Z, Hu L, Mo R, et al. Novel and founder variants of SERPINA12 in Chinese patients with autosomal recessive palmoplantar keratoderma. Br J Dermatol 2022; 187: 267–270. 10.1111/bjd.21064 [DOI] [PubMed] [Google Scholar]
  • 10.Akiyama M. ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts. Hum Mutat 2010; 31: 1090–1096. 10.1002/humu.21326 [DOI] [PubMed] [Google Scholar]
  • 11.Liu Y, Mo R, Chen Z, Yang Y. Novel variants in ABCA12 cause erythrokeratodermia variabilis. Br J Dermatol 2024; 190: 454. 10.1093/bjd/ljad494 [DOI] [PubMed] [Google Scholar]
  • 12.liu Y, Chen ZM, Yang Y. Chanarin–Dorfman syndrome: the first case reported in China. Chin J Dermatol 2021; 54: 673–676. [Google Scholar]
  • 13.Huber M, Rettler I, Bernasconi K, Frenk E, Lavrijsen SP, Ponec M, et al. Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science 1995; 267: 525–528. 10.1126/science.7824952 [DOI] [PubMed] [Google Scholar]
  • 14.Lefévre C, Audebert S, Jobard F, Bouadjar B, Lakhdar H, Boughdene-Stambouli O, et al. Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. Hum Mol Genet 2003; 12: 2369–2378. 10.1093/hmg/ddg235 [DOI] [PubMed] [Google Scholar]
  • 15.Jobard F, Lefèvre C, Karaduman A, Blanchet-Bardon C, Emre S, Weissenbach J, et al. Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. Hum Mol Genet 2002; 11: 107–113. 10.1093/hmg/11.1.107 [DOI] [PubMed] [Google Scholar]
  • 16.Radner FP, Marrakchi S, Kirchmeier P, Kim GJ, Ribierre F, Kamoun B, et al. Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans. PLoS Genet 2013; 9: e1003536. 10.1371/journal.pgen.1003536 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Lefèvre C, Bouadjar B, Ferrand V, Tadini G, Mégarbané A, Lathrop M, et al. Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Mol Genet 2006; 15: 767–776. 10.1093/hmg/ddi491 [DOI] [PubMed] [Google Scholar]
  • 18.Israeli S, Khamaysi Z, Fuchs-Telem D, Nousbeck J, Bergman R, Sarig O, et al. A mutation in LIPN, encoding epidermal lipase N, causes a late-onset form of autosomal-recessive congenital ichthyosis. Am J Hum Genet 2011; 88: 482–487. 10.1016/j.ajhg.2011.02.011 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Lefèvre C, Bouadjar B, Karaduman A, Jobard F, Saker S, Ozguc M, et al. Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet 2004; 13: 2473–2482. 10.1093/hmg/ddh263 [DOI] [PubMed] [Google Scholar]
  • 20.Grall A, Guaguère E, Planchais S, Grond S, Bourrat E, Hausser I, et al. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat Genet 2012; 44: 140–147. 10.1038/ng.1056 [DOI] [PubMed] [Google Scholar]
  • 21.Shigehara Y, Okuda S, Nemer G, Chedraoui A, Hayashi R, Bitar F, et al. Mutations in SDR9C7 gene encoding an enzyme for vitamin A metabolism underlie autosomal recessive congenital ichthyosis. Hum Mol Genet 2016; 25: 4484–4493. 10.1093/hmg/ddw277 [DOI] [PubMed] [Google Scholar]
  • 22.Klar J, Schweiger M, Zimmerman R, Zechner R, Li H, Törmä H, et al. Mutations in the fatty acid transport protein 4 gene cause the ichthyosis prematurity syndrome. Am J Hum Genet 2009; 85: 248–253. 10.1016/j.ajhg.2009.06.021 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Heinz L, Kim GJ, Marrakchi S, Christiansen J, Turki H, Rauschendorf MA, et al. Mutations in SULT2B1 cause autosomal-recessive congenital ichthyosis in humans. Am J Hum Genet 2017; 100: 926–939. 10.1016/j.ajhg.2017.05.007 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Kirchmeier P, Zimmer A, Bouadjar B, Rösler B, Fischer J. Whole-exome-sequencing reveals small deletions in CASP14 in patients with autosomal recessive inherited ichthyosis. Acta Derm Venereol 2017; 97: 102–104. 10.2340/00015555-2510 [DOI] [PubMed] [Google Scholar]
  • 25.Mohamad J, Samuelov L, Malchin N, Rabinowitz T, Assaf S, Malki L, et al. Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population. Exp Dermatol 2021; 30: 1290–1297. 10.1111/exd.14345 [DOI] [PubMed] [Google Scholar]
  • 26.Nagtzaam IF, van Leersum FS, Kouwenberg LCM, Blok MJ, Vreeburg M, Steijlen PM, et al. STS pathogenic variants in a Dutch patient cohort clinically suspected for X-linked ichthyosis show genetic heterogeneity. Br J Dermatol 2022; 187: 820–822. 10.1111/bjd.21775 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Shearer Z, White G, Steed JZ, Brown C, Venable T, Baber M. A novel combination of mutations leading to congenital ichthyosis and ichthyosis vulgaris. Clin Case Rep 2023; 11: e7910. 10.1002/ccr3.7910 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Hotz A, Kopp J, Bourrat E, Oji V, Süßmuth K, Komlosi K, et al. Mutational spectrum of the ABCA12 gene and genotype-phenotype correlation in a cohort of 64 patients with autosomal recessive congenital ichthyosis. Genes (Basel) 2023; 14. 10.3390/genes14030717 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Rossel SVJ, Clabbers JMK, Steijlen PM, van den Akker PC, Spuls PI, Middelkamp Hup MA, et al. Expanding the molecular and clinical spectrum of autosomal recessive congenital ichthyosis caused by pathogenic variants in NIPAL4 and PNPLA1 and evaluation of novel therapeutic interventions. J Eur Acad Dermatol Venereol 2023; 37: e1405–e1409. 10.1111/jdv.19340 [DOI] [PubMed] [Google Scholar]
  • 30.Terrinoni A, Sala G, Bruno E, Pitolli C, Minieri M, Pieri M, et al. Partial loss of function ABCA12 mutations generate reduced deposition of glucosyl-ceramide, leading to patchy ichthyosis and erythrodermia resembling erythrokeratodermia variabilis et progressiva (EKVP). Int J Mol Sci 2023; 24. 10.3390/ijms241813962 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Liu J, Chen ZM, Yang Y. Mutation analysis of the PNPLA1 gene in three families with congenital ichthyosiform erythroderma. Chin J Dermatol 2022; 55: 685–689. [Google Scholar]
  • 32.Rothnagel JA, Dominey AM, Dempsey LD, Longley MA, Greenhalgh DA, Gagne TA, et al. Mutations in the rod domains of keratins 1 and 10 in epidermolytic hyperkeratosis. Science 1992; 257: 1128–1130. 10.1126/science.257.5073.1128 [DOI] [PubMed] [Google Scholar]
  • 33.Rothnagel JA, Traupe H, Wojcik S, Huber M, Hohl D, Pittelkow MR, et al. Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens. Nat Genet 1994; 7: 485–490. 10.1038/ng0894-485 [DOI] [PubMed] [Google Scholar]
  • 34.Choate KA, Lu Y, Zhou J, Choi M, Elias PM, Farhi A, et al. Mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10. Science (New York, NY) 2010; 330: 94–97. 10.1126/science.1192280 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Pan Y, Feng C, Wang H, Lee M, Tang Z, Lin Z. Ichthyosis with confetti caused by new and recurrent mutations in KRT10 associated with varying degrees of keratin 10 mis-localization. J Dermatol Sci 2020; 98: 35–40. 10.1016/j.jdermsci.2020.02.005 [DOI] [PubMed] [Google Scholar]
  • 36.Chavanas S, Bodemer C, Rochat A, Hamel-Teillac D, Ali M, Irvine AD, et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 2000; 25: 141–142. 10.1038/75977 [DOI] [PubMed] [Google Scholar]
  • 37.Huang X, Chen Z-M, Yang Y. Homozygous nonsense mutation in SDR9C7 in a Chinese patient with autosomal recessive congenital ichthyosis. Int J Dermatol Venereol 2023; 6: 52–54. 10.1097/JD9.0000000000000236 [DOI] [Google Scholar]

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