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. 2016 Nov 23;5(1):85-91.
doi: 10.1002/mgg3.263. eCollection 2017 Jan.

CLN8 disease caused by large genomic deletions

Clare Beesley  1 , Rita J Guerreiro  2 , Jose T Bras  2 , Ruth E Williams  3 , Ana Lia Taratuto  4 , Christin Eltze  5 , Sara E Mole  6
Affiliations

CLN8 disease caused by large genomic deletions

Clare Beesley et al. Mol Genet Genomic Med. .

Abstract

Background: The presence of deletions can complicate genetic diagnosis of autosomal recessive disease.

Method: The DNA of patients was analyzed in a diagnostic setting.

Results: We present three unrelated patients each carrying deletions that encompass the 37 kb CLN8 gene and discuss their phenotype. Two of the cases were hemizygous for a mutant allele - their deletions unmasked a mutation in CLN8 on the other chromosome.

Conclusion: Microarray analysis is recommended in any patient suspected of NCL who is apparently homozygous for a mutation that is not present in one of the parents or when the family has no known consanguinity.

Keywords: Batten; CLN8; NCL; neuronal ceroid lipofuscinosis.

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Figures

Figure 1
Figure 1
Results for chromosome 8 from whole genome genotyping represented by the log ratio in the bottom and B allele frequencies on the top panels. The green vertical bar indicates the location of CLN8 in chromosome 8. A large homozygous deletion on 8p23.3 encompassing CLN8 can be identified in Child A by the abrupt decline in the log ratio accompanied by randomly placed markers in the B allele frequency showing no specific hybridization with any probe in the array (Reference sequence: NM_001042432.1).
Figure 2
Figure 2
The upper panel is the array CGH result showing the heterozygous copy number loss of ~54 kb at 8p.23.3, which encompasses the CLN8 gene (circled in red). The lower panel shows the Sanger sequencing results for the “hemizygous” c.728T>C, p.(Leu243Pro) novel variant in Child C. Upper and lower panels are the normal sequence (forward & reverse) and the middle panels are the patient (forward and reverse) (Reference sequence: NM_001042432.1).
Figure 3
Figure 3
Sanger sequencing results for Child C showing the “hemizygous” c.763C>T, p.(Gln255*) mutation. Top and bottom panels are the normal sequence (forward and reverse) and the middle panels are the patient (forward and reverse) (Reference sequence: NM_001042432.1).
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