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Reports on a case of a male infant with neonatal encephalopathy and a de novo MECP2 mutation. Description of the clinical features of the infants that raised suspicion of MECP2 dysfunction; Observation of the occurrence of mutation on the maternally inherited X chromosome.

A female patient presented with features atypical of Friedreich ataxia(FA). For many years she was considered to have inflammatory demyelination rather than a pure cerebellar syndrome. Presenting in her late 20's, she has no scoliosis and no evidence for peripheral neuropathy or pes cavus. When testing for a series of SCA mutations proved negative, a diagnosis of FA was considered and she tested positive for the GAA expansion mutation within the frataxin gene. No normal sized allele was present and hence she was considered to be homozygous for the expansion and this was reported as being the underlying cause of her clinical symptoms. Surprisingly, later tests showed that her biological daughter, and therefore, an obligate carrier, did not have an expanded allele. Further studies have demonstrated that this apparent non-maternity is explained by the presence of a deletion on one of the mother's alleles and this has been passed to the daughter. This case illustrates that hemizygous deletions within the frataxin gene may be associated with atypical FA. Caution should, therefore, be observed when counselling and testing relatives if the index case in a FA family appears to be homozygous for a GAA expansion mutation. [ABSTRACT FROM AUTHOR]

Currarino syndrome is an autosomal dominant form of sacral agenesis, that is caused by mutation of the homeobox gene, MNX1 (previously HLXB9). The pathology shows variability, with some patients being clinically asymptomatic with partial sacral dysgenesis. This involves the formation of a hemisacrum with preservation of the 1st sacral vertebrae. Severe cases have the hemisacrum together with a presacral mass and anorectal stenosis. Previous studies at the Institute of Human Genetics, University of Newcastle upon Tyne, identified 22 families with likely pathogenic mutations in the MNX1 gene. A variety of nonsense, frameshift, missense, deletion and insertion mutations, spread throughout the three exons of the gene, were described. The aim of this study was to develop a robust molecular diagnostic service for patients with Currarino syndrome. This has involved confirmation of the mutations identified in the research project by sequencing and other mutation specific tests such as primer extension, and the use of known mutation controls to make a comparison between standard SSCP and DHPLC as mutation detection tools. A clinical questionnaire has been designed to help clinicians determine the appropriateness of their referrals and to filter referrals. The results of this study have been used to establish a diagnostic protocol for this syndrome. [ABSTRACT FROM AUTHOR]

Examines the embryonic expression of the HLXB9 currarino syndrome gene. Effect of missense mutations on patient condition; Proposal of a notochordal defect in the tail bud; Implication of the HLXB9 expression on the developing gut.