14q(22) deletion in a familial case of anophthalmia with polydactyly

Abstract

We report a family of anophthalmia with ocular and extraocular manifestations. The proband, his three sisters, and two sons had anophthalmia and preaxial polydactyly in the right hand. Cytogenetic analysis was done for the proband and two of his sons, one of whom was affected. Another male child was affected but was not available for cytogenetic analysis. Karyotypes of both affected individuals showed deletion on long arm of 14q22q23. Literature review shows four cases of anophthalmia with extra ocular anomalies associated with 14q (q22q23) deletion. Recently it has been suggested that the human homeobox gene, SIX6, and the BMP-4 gene are responsible for eye development. Both are located in the chromosome 14q22.3-q23 region. Deletion in this region has been known to be associated with anophthalmia and pituitary anomalies. This is the first family of anophthalmia, which showed polydactyly with a chromosomal deletion in the 14q22-q23 region and its familial transmission in two generations with a total of six affected individuals.

Proper differentiation of photoreceptors and amacrine cells depends on a regulatory loop between NeuroD and Six6

“…This cooperation, together with the observation that Lhx2 and Pax6 regulate Six6 expression in mammals (Tetreault et al, 2009), constitutes a starting point towards the full identification of the transcriptional network controlling mammalian Six6 function. This, in turn, might help define the molecular causes of human inborn eye defects such as anophthalmia, microphthalmia and coloboma, which have been associated with genetic alterations of the SIX6 locus (Ahmad et al, 2003;Gallardo et al, 1999;Gallardo et al, 2004).…”

Pericentric inversion, inv(14)(p11.2q22.3), in a 9-month old with features of Goldenhar syndrome

“…Chromosome rearrangements involving the 14q22q23 region are rare with only a few interstitial deletions and one interstitial duplication reported (Bennett et al, 1991;Elliott et al, 1993;Lemyre et al, 1998;Ahmad et al, 2003;Nolen et al, 2006;Ou et al, 2008). All patients with interstitial 14q22q23 rearrangements show a common phenotype that includes bilateral anopthalmia, ear anomalies, microretrognathia, arched palate, facial asymmetry, and microcephaly.…”

Mosaic monosomy 14: clinical features and recognizable facies

“…A review of the literature showed five cases of anophthalmia with extraocular anomalies associated with 14q(q22q23) deletion: Bennett et al (1991), Elliott et al (1993), Phadke et al (1994), Lemyre et al (1998) and Ahmad et al (2003). Lemyre et al (1998), suggested that the region 14q22 is important for eye and pituitary development and human BMP-4 gene, a growth factor member of the TGF-b superfamily, maps to 14q22-23 and may play a role in pituitary and eye development.…”