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Supplementary Figure and Table Legends
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Suppl. Figure 1
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Workflow for analysis of exome sequence data. Variant prioritisation criteria: (i)
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variants were non-synonymous (includes nonsense, frameshift and missense) or splice
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site variants, (ii) variants did not occur with a frequency of ≥ to 1% in 1000genomes,
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ESP5400 or dbSNP (unless they were a previously defined pathogenic blindness variant
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in dbSNP), (iii) variants were covered by at least 10 reads with at least 20% variation
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reads or at least 5 reads with at least 40% variation reads, and (iv) variants were
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considered “probably pathogenic” on the basis of the type of mutation and our in silico
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analysis criteria.
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Suppl. Figure 2
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Pedigrees and Sanger sequence analysis in families with pathogenic variants and
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segregation indicating autosomal dominant or recessive inheritance patterns. Variants
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are indicated by a blue vertical line.
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Family 1: De novo heterozygous mutation in GJA8 in II.1 (Patient 1), not present in her
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parents and passed onto the offspring in an autosomal dominant manner.
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Family 4: Heterozygous mutation in CRYGC in I.2 (Patient 4), passed onto the children
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in an autosomal dominant manner.
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Family 5: Compound heterozygous mutations in CYP1B1 in II.1 (Patient 5) that have
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been inherited in an autosomal recessive manner from each of her unaffected parents
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who are heterozygous for each of the mutations.
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Family 6: De novo heterozygous mutation in PAX6 in II.1 (Patient 6), and not present in
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either of her parents.
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Sequences are shown in forward direction, apart from CRYGC sequence in Family 4
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which is in reverse. + symbol indicates a normal, non-variant allele. Reference
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sequences
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NM_000104.3; PAX6, NM_000280.4.
used:
GJA8,
NM_005267.4;
CRYGC,
NM_020989.3;
CYP1B1,
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Suppl. Figure 3
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Pedigrees and Sanger sequence analysis in families with variants with incomplete
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penetrance or inheritance pattern not consistent with the disease phenotype.
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Family 3: Heterozygous variant in CRYBA1 in II.1 (Patient 3), also present in her
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unaffected mother.
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Family 9: Compound heterozygous variants in CYP1B1 in II.1 (Patient 9), that have
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been inherited in an autosomal recessive manner from each of her unaffected parents
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who are heterozygous. Her affected brother is heterozygous for one of the CYP1B1
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variants. Heterozygous variant in BFSP1 in II.1 (Patient 9), that is also present in her
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affected brother and her unaffected mother.
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Family 10: Heterozygous variant in ABCB6 in II.1 (Patient 10), which is also present in
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his unaffected father. Heterozygous variant in SLC16A12 in II.1 (Patient 10), which is
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also present in his unaffected mother.
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Family 11: Heterozygous variant in GDF3 in II.1 (Patient 11), which is also present in
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his unaffected father. Compound heterozygous variants in CYP1B1 in II.1 (Patient 11),
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that have been inherited in an autosomal recessive manner from each of his unaffected
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parents who are heterozygous. Heterozygous variant in BFSP1 in II.1 (Patient 11),
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which is present in his unaffected mother and his unaffected father.
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Sequences are shown in forward direction, apart from CRYBA1 sequence in Family 3,
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SLC16A12 sequence in Family 10, and GDF3 and BFSP1 sequences in Family 11
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which are in reverse. + symbol indicates a normal non-variant allele.
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Reference sequences used: CYP1B1, NM_000104.3; CRYBA1, NM_005208.4; BFSP1,
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NM_001161705.1; ABCB6, NM_005689.2; SLC16A12, NM_213606.3; and GDF3,
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NM_020634.1
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Suppl. Table 1
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56 developmental eye disease genes examined in this study.
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Suppl. Table 2
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Clinical ocular phenotypes in patients undergoing exome sequencing and family
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members.
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Suppl. Table 3
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Exome sequencing analysis and variant prioritisation for developmental eye disease
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gene identification.
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