Cataracts, ataxia, short stature, and mental retardation in a Chinese family mapped to Xpter-q13.1

Abstract

Six males in a Chinese family affected by congenital cataracts, cerebellar ataxia, short stature, and mental retardation, which were tentatively named CASM syndrome. Eight female carriers in the family had cataracts alone. Linkage analysis demonstrated that the disease is transmitted through X-linked inheritance, either by setting the syndrome in males as an X-linked recessive trait, or by setting cataracts in the family as an X-linked dominant trait. The gene responsible for the syndrome is mapped to XpterXq13.1, with the highest lod score of 3.91 for DXS1226, DXS991, and DXS1213 at h = 0. Haplotype analysis identified that the allele harboring the disease gene cosegregated with all female carriers as well as affected males in the family. Clinically and genetically, the disease in this family is different from any known disease. Major features of CASM syndrome that distinguish it from other diseases are X-linked inheritance and cataracts in carrier females.

KITLG Mutations Cause Familial Progressive Hyper- and Hypopigmentation

“…Because of small pedigree size, we did not have the statistical power to test this in these families. Locus heterogeneity for FPH has also been reported, as one FPH family was linked to 19p (Guo et al, 2006). Because of the phenotypic similarity, the gene in this locus likely acts in the KITLG/c-KIT signalling pathway (Figure 5).…”

“…In contrast, the hypopigmented-appearing maculae show a slight basal hyperpigmentation of the epidermis, with virtually no melanophages in the upper dermis (Stuhrmann et al, 2008;Wang et al, 2009). Two loci have been identified for FPH: one on chromosome 19p13-pter (Guo et al, 2006) and another on 12q21.31-q23.1 (Wang et al, 2009). DUH2 was subsequently linked to the latter (Bukhari et al, 2006;Stuhrmann et al, 2008).…”

Ocular findings and genomics of X-linked recessive disorders: A review

“…CASM (OMIM #300619) is an X-linked recessive disorder and maps at Xpter-q13.1 locus, containing the disease and co-segregating with the cataract phenotype in both sexes. [ 38 ]…”

“…It is often characterized by muscle hypotonia, mild-to-moderate mental retardation, postural tremor and weakness in males. [ 38 ] Ocular findings include cataracts in both sexes with opacification being more extensive in males. [ 38 ] Affected females reported blurred vision, pulverulent and punctate lens opacities with posterior subcapsular sclerosis.…”

“…[ 38 ] Ocular findings include cataracts in both sexes with opacification being more extensive in males. [ 38 ] Affected females reported blurred vision, pulverulent and punctate lens opacities with posterior subcapsular sclerosis. Anterior chamber, iris, pupils and cornea were normal.…”