Segregation of the fragile-X mutation from an affected male: Evidence of unusual somatic instability in the FMR-1 locus

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134230

Kambouris, M; Bluhm, D; Feldman, G L ^[1]

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1. Henry Ford Hospital, Detroit, MI (United States); and others

Fragile X syndrome is associated with an unstable CGG-repeat in the FMR-1 gene. There are few reports of affected males transmitting the FMR-1 gene to offspring. We report a family in which the paternal grandfather has an unusual FMR-1 pattern, with allele sizes ranging from premutation to full mutation. The family was initially ascertained because of a diagnosis of fragile X syndrome in this individual`s grandson. For Southern blot analyses, the samples were digested with Pst 1 and hybridized to the pE5.1 probe or digested with HindIII and hybridized to the StB12.3 probe. The proband had a high molecular weight allele, indicating significant amplifications, and an abnormal methylation pattern, consistent with a full mutation. His twin sister, who also had features of fragile X syndrome, had a similar pattern in addition to her normal allele (30 repeats). Their mother had one normal allele (33 repeats) and a premutation allele (>130 CGG repeats), with a normal methylation pattern. The maternal grandmother had alleles of 32 and 33 CGG repeats. These findings support the hypothesis that transmission of a full fragile-X mutation does not occur through a male, even if that male has clincial and molecular evidence of a full mutation. Gonadal mosaicism is an alternative explanation. Thus, an affected male with extensive FMR-1 somatic mosaicism transmitted a large premutation to his daughter, who in turn transmitted a full mutation to both of her offspring. FMR-1 protein studies on this individual, which are in progress, should help to determine the correlation, if any, of the molecular findings with the phenotypic effects.

• OSTI ID: 134230
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CORRELATIONS
DNA HYBRIDIZATION
GENE AMPLIFICATION
GENE MUTATIONS
GENES
GENETICS
GENOTYPE
GONADS
HEREDITARY DISEASES
HUMAN X CHROMOSOME
INSTABILITY
MALES
MENTAL DISORDERS
METHYLATION
MOSAICISM
NUCLEOTIDES
PHENOTYPE
POLYMERASE CHAIN REACTION
PROBES
SIZE
SOMATIC MUTATIONS