Figure 1

Genetic Analysis of Three Families with Members Affected by Microphthalmia with Limb Anomalies

(A) Pedigrees of the three families.

(B) Linkage analysis with SNPs and microsatellite markers on chromosome 14. From left to right: chromosome ideogram, genetic markers, linked regions of the three families, and genes mapped to the shortest overlapping linked region (between AFM114YH10 and Ch14-STS6 [UCSC coordinates, Feb. 2009: chromosome 14: 68,388,190–71,347,908 bp]).

(C) Sequences of mutations identified in each family. Affected patients in family A have a homozygous nonsense mutation (c.718C>T). Patients in families C and X have distinct homozygous splice-donor site mutations (c.664+1G>A and c.378+1G>A, respectively). For all mutations, parents of affected patients are heterozygous carriers, without exception. Sequences of the exon and intron are presented in upper and lower cases, respectively.

(D) At the top is a depiction of a schematic representation of SMOC1 consisting of 12 exons (UTR and coding exons are indicated by open and filled rectangles, respectively). The locations of three mutations are indicated by red dots. At the bottom, the functional domains of SMOC1 are depicted. Abbreviations are as follows: FS, the follistatin-like domain; TY, the thyroglobulin-like domain; SMOC, the domain unique to SMOC; and EC, the extracellular calcium-binding domain.