ABSTRACT
Here we report on a Brazilian female patient with the clinical manifestations of the holoprosencephaly-like phenotype who also presented with a retroocular granuloma diagnosed as Langerhans cell histiocytosis in early infancy. Mutation analysis showed a missense mutation (G316D) in the exon 2 of SIX3 gene, which was predicted as damaged by the PolyPhen program. We discuss the clinical and genetic aspects of this unusual case.
Subject(s)
Eye Proteins/genetics , Heterozygote , Histiocytosis, Langerhans-Cell/complications , Histiocytosis, Langerhans-Cell/genetics , Holoprosencephaly/complications , Holoprosencephaly/genetics , Homeodomain Proteins/genetics , Mutation, Missense/genetics , Nerve Tissue Proteins/genetics , Adult , Amino Acid Substitution/genetics , Brazil , Female , Histiocytosis, Langerhans-Cell/diagnosis , Holoprosencephaly/diagnosis , Humans , Magnetic Resonance Imaging , Phenotype , Homeobox Protein SIX3ABSTRACT
Holoprosencephaly (HPE) is a malformation sequence where the cerebral hemispheres fail to separate into distinct left and right halves. It can be associated with midline structural anomalies of the central nervous system and/or face. SHH is the major gene implicated in HPE and it plays a critical role in early forebrain and central nervous system development. SHH is expressed in the human embryo in the notochord, the floorplate of the neural tube, and the posterior limb buds. In the present study we performed mutational analysis of the entire coding region of the SHH gene in 37 unrelated individuals with the HPE spectrum. Three different variants were found throughout the extent of the gene. No genotype-phenotype correlation is evident based on the type or position of the mutations. This study confirms the great genetic heterogeneity of the disease and the difficulty to establish genotype-phenotype correlations.
Subject(s)
Genetic Predisposition to Disease , Hedgehog Proteins/genetics , Holoprosencephaly/genetics , Mutation/genetics , DNA Mutational Analysis/methods , Female , Glutamine/genetics , Histidine/genetics , Holoprosencephaly/pathology , Humans , Magnetic Resonance Imaging/methods , MaleABSTRACT
We describe a Brazilian boy with semilobar holoprosencephaly, ectrodactyly, bilateral cleft of lip and palate, and severe mental retardation. The karyotype was normal and the screening for mutations in the genes SHH, TGIF, SIX3, GLI2, TP73L, and DHCR7 did not show any change. This rare condition was described previously in seven male patients. Clinical and genetic aspects are discussed.
