Uniparental disomy as an unexpected cause of Meckel-Gruber syndrome: report of a case.

Background: Meckel-Gruber syndrome (MKS, OMIM #607361) is a rare pre- or perinatal lethal autosomal recessive ciliopathy caused by mutations in at least 12 known genes. It has a clinical and genetic overlap with other viable ciliopathies, especially Joubert syndrome and Joubert syndrome-related disorders. MKS is characterized by multicystic kidney dysplasia, central nervous system malformations (usually occipital encephalocele), ductal plate malformation of the liver, and postaxial polydactyly.

Primary osteomyelofibrosis and an XX-male genotype.

A 62-yr-old man with two healthy daughters was diagnosed with osteomyelofibrosis. To our surprise, a female XX-karyotype was observed in bone marrow and confirmed in PHA-stimulated T-lymphocytes from peripheral blood. Further molecular genetic investigation revealed a submicroscopic translocation between the short arm of X and Y, which leads to an XX-male genotype based on an unbalanced translocation X;Y.

Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and further expand the clinical spectrum of holoprosencephaly.

Schizencephaly (SCH) is a clinically and etiologically heterogeneous cerebral malformation presenting as unilateral or bilateral hemispheric cleft with direct connection between the inner and outer liquor spaces. The SCH cleft is usually lined by gray matter, which appears polymicrogyric implying an associated impairment of neuronal migration. The majority of SCH patients are sporadic, but familial SCH has been described.

A new gene family (FAM9) of low-copy repeats in Xp22.3 expressed exclusively in testis: implications for recombinations in this region.

Illegitimate recombinations between low-copy repetitive elements (LCR) have been implicated in the pathogenesis of various chromosomal rearrangements. Two such duplicons have been reported previously on Xp22.3, the CRI-S232 elements, involved in the generation of deletions in the steroidsulfatase gene and five members of the G1.