Identification of de Novo and Novel Mutations in LTBP2 in Pakistani Families with Inherited Primary Congenital Glaucoma
Identification of de Novo and Novel Mutations in LTBP2 in Pakistani Families with Inherited Primary Congenital Glaucoma
Rani Saira Saleem1*, Muhammad Imran Khan2, Saba Irshad1*, Sorath Noorani Siddiqui3 and Shazia Micheal4
Fig. 1.
Family I: LTBP2 de Novo Mutation c.1762_1763del; p. (Leu588Valfs*14).
(A) A two-generation family pedigree. PB (II: 1) is indicated with an arrowhead. Affected members are indicated with black filled box. (B) sanger sequence analysis of the de novo mutation showing the chromatograms of unaffected father, Mother and the affected son.
Fig. 2.
Family II: LTBP2 canonical splice site mutation (c.2531-2A>C).
(A) Homozygosity mapping in two affected and two unaffected individuals of family II. Analysis was done by using online web tool homozygosity mapper (http://www.homozygositymapper.org/). The red line indicates the homozygous regions in the SNP array analysis, one of them corresponding to 22Mb region at chromosome 14 for LTBP2. (B) Pedigree of consanguineous family II showing segregation of a novel mutation c.2531-2A>C. Proband is indicated by a black arrowhead. (C) Chromatogram showing Sanger sequencing results for the canonical splice site mutation c.2531-2A>C indicated with respect to homozygous normal (IV:1), heterozygous carrier (III:1) and homozygous mutant (IV:2). (D) In-Silico predictions for mutation (c.2531-2A>C) by ALAMUT Visual. The score for natural 3’ splice site was decreased in the mutant.
Fig. 3.
Family III: LTBP2, synonymous splice site c.1686G>A; p. (Gln562Gln) mutation.
(A) Homozygosity mapping in three affected and three unaffected individuals of family III. Analysis was done by using online web tool Homozygosity mapper (http://www.homozygositymapper.org/). The red line indicates the homozygous regions in the SNP array analysis, one of them corresponding to 14Mb region at chromosome 14 for LTBP2. (B) Pedigree of consanguineous family III showing segregation of a novel c.1686G>A mutation. Proband indicated by a black arrowhead. (C) Chromatogram showing Sanger sequencing results for the splice donor site mutation c.1686G>A indicated with respect to homozygous normal (IV: 6), heterozygous carrier (III: 4) and homozygous mutant (IV: 7). (D) In-Silico predictions for mutation c.1686G>A; p. (Gln562Gln) by ALAMUT Visual. The score for natural 5’ splice site was decreased in the mutant. Respective HSF and SSF scores have also been listed in the table.
Fig. 4.
Structural representation of LTBP2 exons showing the N and C-Terminal of the protein. The exons with previously reported mutations have been shown in rust red color. Current study mutations and exons have been marked with red and black color, respectively.
