Neuronal Ceroid Lipofuscinosis 14 via the KCTD7 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
3809 KCTD7 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3809KCTD781479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

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Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

The neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative lysosomal storage disorders caused by the accumulation of ceroid and lipofuscin in various cell types, mainly cells of the cerebral cortex, cerebellar cortex, and retina (Dyken et al. 1988; Williams and Mole 2012). Characteristic features at onset include clumsiness; deterioration of vision and psychomotor functions; seizures and behavioral changes. Progression of clinical features results ultimately in total disability, blindness and premature death. Although NCL affects primarily children, age of onset of symptoms varies from infancy to adulthood. The incidence of NCL is variable and ranges from 1.3 to 7 per 100,000 (Mole and Williams 2013). However, it is more common in northern European populations, particularly Finland where the incidence may reach 1 in 12,500 individuals and a carrier frequency of 1 in 70 (Rider and Rider 1988). NCLs are clinically and genetically heterogeneous. A nomenclature and classification based both on the age of onset of symptoms and the disease-causing gene has been recently developed, which classifies NCLs into thirteen subtypes (CLN1-8, 10-14) (Williams and Mole 2012). The causative gene for the CLN9 phenotype has not been identified yet (Schulz et al. 2004).

Of note, NCLs were previously known as Batten disease. However, in recent nomenclature, Batten disease only applies to NCL caused by pathogenic variants in CLN3.

To date, one single CLN14 family with two affected individuals has been reported in the literature. Symptoms started during the first year of life with seizures. Speech and motor involvements were evident by the second year. As the disease progressed, additional symptoms appeared and included visual impairment, microcephaly, and loss of motor reflexes. MRI findings indicated global cortical atrophy, thinning of the corpus callosum, and loss of subcortical white matter. In this family, the diagnosis of neuronal ceroid lipofuscinosis was confirmed by the presence of osmiophilic storage material in peripheral blood skin biopsy (Staropoli et al. 2012).

Genetics

Most CLNs, including CLN14, are inherited in an autosomal recessive manner. Thirteen genes have been implicated in the disorder: PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8, CTSD, DNAJC5, CTSF, ATP13A2, GRN, and KCTD7 (Mole and Williams 2013).

To date, only one consanguineous family with two affected sibs is reported to have pathogenic KCTD7 variants (Staropoli et al. 2012). In this family, a homozygous missense variant (c.550C>T, p.Arg184Cys) was reported to be disease-causing. Evidence for pathogenicity included its co-segregation with the disease; its absence from two large population databases of genetic variations (1000 Genomes Project and Exome Variant Server); and a predicted deleterious effect by several prediction tools.

Pathogenic KCTD7 variants have been previously reported in patients with progressive myoclonic epilepsy (PME), with no evidence of lysosomal storage material (Van Bogaert et al. 2007).

The KCTD7 gene encodes potassium channel tetramerization domain containing protein 7, which is postulated to have a role in the regulation of ion channels. However, its precise function is unknown at this time (Azizieh et al. 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in KCTD7 appear to be a rare cause of NCL. Only one NCL family with a pathogenic KCTD7 variant has been reported to date (Staropoli et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the KCTD7 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for the KCTD7 test are patients with a clinical diagnosis suggestive of neuronal ceroid lipofuscinosis and no pathogenic variants in the remaining NCL genes. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in KCTD7.

Gene

Official Gene Symbol OMIM ID
KCTD7 611725
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Neuronal Ceroid Lipofuscinoses (Batten Disease) Panel

Citations

  • Azizieh R. et al. 2011. Molecular Neurobiology. 44: 111-21. PubMed ID: 21710140
  • Dyken P.R. 1988. American journal of medical genetics. Supplement. 5: 69-84. PubMed ID: 3146331
  • Mole S.E., Williams R.E. 2013. Neuronal Ceroid-Lipofuscinoses. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301601
  • Rider J.A., Rider D.L. 1988. American journal of medical genetics. Supplement. 5: 21-6. PubMed ID: 3146319
  • Schulz A. et al. 2004. Annals of neurology. 56: 342-50. PubMed ID: 15349861
  • Staropoli J.F. et al. 2012. American Journal of Human Genetics. 91: 202-8. PubMed ID: 22748208
  • Van Bogaert P. et al. 2007. Annals of Neurology. 61: 579-86. PubMed ID: 17455289
  • Williams R.E., Mole S.E. 2012. Neurology. 79: 183-91. PubMed ID: 22778232

Ordering/Specimens

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Specimen Types

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