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Long-Read Sequencing 

Comprehensive Analysis of Incontinentia Pigmenti (CAIP)

Utimate Testing for Patients with Suspected Incontinentia Pigmenti, or Their Relatives

Disease Information and Challenges of Detection

Incontinentia pigmenti (IP), also known as Bloch–Sulzberger syndrome, is an X-linked dominant multisystem ectodermal dysplasia that primarily affects the skin, eyes, teeth, hair, nails, and central nervous system. IP is typically lethal in males, while approximately 95% of affected individuals are female. Clinical manifestations in females are highly variable, ranging from classic neonatal skin lesions to ocular, dental, neurologic, and developmental complications.

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The IKBKG gene (also known as NEMO) is the only gene currently known to be associated with IP. The IKBKG exon 4–10 deletion accounts for approximately 80% of female IP cases and is commonly detected by qPCR or MLPA. However, identifying the remaining pathogenic variants can be technically challenging with conventional sequencing methods, including Sanger sequencing, short-read NGS, due to interference from the highly homologous pseudogene IKBKGP1 (which shares more than 99% sequence homology across exons 3–10).

Summary of the major limitations of routine IP geneitc testing methods:

Testing Method

Detection Scope

Key Limitations

LR-PCR + gel electrophoresis

Detects exon 4–10 deletion

Cannot simultaneously detect SNVs/InDels and cannot precisely define breakpoint locations

MLPA

Detects exon 4–10 deletion and exon-level CNVs

May not resolve exact breakpoints

Sanger sequencing

Detects SNVs/InDels

Susceptible to pseudogene interference and cannot detect large deletions

LR-PCR + NGS anaylsis

Detects SNVs/InDels and exon 4–10 deletion

Susceptible to pseudogene interference and may produce false results

WES/ WGS

Detects SNVs, InDels, and some structural variants

Susceptible to pseudogene interference and may produce false results

The Ultimate Solution with LRS

To address these limitations, we offer LRS-based testing for comprehensive analysis of IP (CAIP). This assay enables full-length analysis of IKBKG and the homologous IKBKGP1 region, helping to distinguish true pathogenic variants from pseudogene-derived signals. By detecting multiple variant types—including SNVs, InDels, structural variants, large deletions, and complex rearrangements—this one-stop test. This helps clinicians reduce diagnostic uncertainty and streamline patient care.

Key Advantage

High Confidence Variant Calling

Full-length analysis of IKBKG and the homologous pseudogene IKBKGP1 helps minimize pseudogene interference and improves variant interpretation confidence

Comprehensive Detection

Detects a broad spectrum of clinically relevant variant types, including SNVs, InDels, large deletions, structural variants, and complex rearrangements

One-Stop Testing Workflow

Provides a single, streamlined assay that overcomes the limitations of stepwise testing, helping reduce testing complexity and streamline patient care

Send-out Testing

When considering our send-out sequencing services:

  1. Consultation: Contact our team for the most current test specifications.

  2. Sample Preparation: Check sample types and shipment requirements to ensure high-quality results. Please check your local export regulations and logistics partners.

  3. Submission: Contact Xcelom when placing an order. Include the completed Test Request and Consent Form, along with any required documents.

Sample Requirements

Peripheral Blood: 2 mL in EDTA tube

Dried Blood Spot (DBS): 3 spots, ≥ 8mm diameter each

Long-fragment gDNA

Transport Conditions

2-8℃, arrive within 72 hours

Testing Scope

Detects the IKBKG variants associated with Incontinentia Pigmenti, including:

  • P, LP, and some VUS SNVs/InDels

  • Selected large intragenic deletions classified as P/LP/VUS

  • Selected complex rearrangements

Turnaround Time (TAT)

15 working days

End-to-End Technology Transfer

Berry Genomics and Xcelom provide dedicated technology transfer package to bring this capability into your laboratory. We offer end-to-end support, including:

  • Lab Setup: Consultation on workflow, equipment, and kits

  • Training: Comprehensive wet-lab training for your staff

  • Bioinformatics Support: Our tailored software solutions streamline variant annotation and interpretation, automatically integrating public databases to assist with ACMG analysis

Resources

References:

1. Consortium For The Application Of Single-Molecule Real-Time Sequencing For The Precision Medicine And Control Of Thalassemia, Group Of Clinical Genetics Medical Genetics Branch Of Chinese Medical Doctor Association, Wu L. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025;42(4):385-396.

2. Liang Q, Gu W, Chen P, et al. A More Universal Approach to Comprehensive Analysis of Thalassemia Alleles (CATSA). J Mol Diagn. 2021;23(9):1195-1204.

3. Huang R, Liu Y, Xu J, et al. Back-to-Back Comparison of Third-Generation Sequencing and Next-Generation Sequencing in Carrier Screening of Thalassemia. Arch Pathol Lab Med. 2024;148(7):797-804.

4. Li S, Hua R, Han X, et al. Targeted long-read sequencing facilitates effective carrier screening for complex monogenic diseases including spinal muscular atrophy, α-/β-thalassemia, 21-hydroxylase deficiency, and fragile-X syndrome. J Transl Med. 2025;23(1):307.

5. Liang Q, He J, Li Q, et al. Evaluating the Clinical Utility of a Long-Read Sequencing-Based Approach in Prenatal Diagnosis of Thalassemia. Clin Chem. 2023;69(3):239-250.

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