Mis-splicing of the GALNS gene resulting from deep intronic mutations as a cause of Morquio a disease

BMC Medical Genetics

Table 2 GALNS nucleotide sequence variants with potential significance in the generation of the GALNS aberrant splicing products detected in Pt2 and Pt3

Chr: Pos (GRCh37.p13)	Zygosity	Parental Zygosity	Variant Type	Identifier (dbSNP 149, NCBI)	Exon/Intron	MAF	HSF Summary/CADD score
Pt2
16:88898099	Heterozygous	Paternal (heterozygous)	c.1002 + 307G > C	rs866140272	INTRON 9	–	ESE gain and alterations to various ESRs - CADD 3.002
Pt3
16:88901744	Heterozygous	Paternal (heterozygous)	c.775C > A; p.Arg259Arg	rs61742258	EXON 8	0.002	Cryptic donor splice site created, ESE loss and ESS gain - CADD 14.49
16:88901827	Heterozygous	Maternal (heterozygous)	c.759-67G > A	rs565875595	INTRON 7	0.001	ESE gain and ESS loss - CADD 6.652
16:88902194	Heterozygous	Paternal (heterozygous)	c.697G > A; p.Asp233Asn	rs753051547	EXON 7	–	Alteration of an exonic ESE site - CADD 24.1
16:88905035	Heterozygous	Maternal (heterozygous)	c.423-862C > T	–	INTRON 4	–	Cryptic donor splice site created - CADD 0.094

- = not present in gnomAD browser beta (http://gnomad.broadinstitute.org/); MAF = minor allele frequency; ESE = exonic splicing enhancer; ESS = exonic splicing silencer; ESRs = exonic splicing regulatory sequences; HSF (Human Splicing Finder) predictions = a tool which assesses the potential impact of these variants on the mRNA splicing phenotype (http://www.umd.be/HSF3/); CADD = Combined Annotation Dependent Depletion = a tool for scoring the deleteriousness of single nucleotide variants as well as insertion/deletion variants in the human genome. A CADD score of > 10 is applied as a threshold to identify high-confidence disease-causing mutations [27]

ISSN: 1471-2350