Severe mental retardation and macroorchidism without mutation in the FMR1 gene

Journal Article · Fri Aug 09 00:00:00 EDT 1996 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/(SICI)1096-8628(19960809)64:2<408::AID-AJMG35>3.3.CO;2-L· OSTI ID:478899

Reyniers, E; De Boulle, K; Storm, K ^[1]

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1. Univ. of Antwerp (Belgium); and others

Only one missense mutation, an Ile304Asn, has been reported in the fragile X gene (FMR1). This mutation is located in the second KH domain of FMR1, and has led to the discovery of the function of the FMR1 gene product as an RNA-binding protein. The patient carrying this mutation has profound mental retardation, macroorchidism, and an {open_quotes}acromegalic{close_quotes} face with prominent supraorbital ridges, enlarged jaw, heavy brow ridges, thick lips, and a broad nose. We have studied the possible involvement of FMR1 in two maternal half-brothers with a phenotype similar to that of the patient with the Ile304Asn mutation. Both brothers had an identical number of CGG repeats in the normal size-range, and shared the same maternal Xq27 haplotype. Southern blot analysis with two overlapping FMR1 cDNA clones, spanning the total FMR1 open reading frame, showed no major deletions, insertions, or gross rearrangements. Single-strand conformation pattern (SSCP) analysis of the KH domains showed no aberrant patterns. The total open reading frame of the FMR1 gene was cloned and sequenced, but no mutation was found. Northern blot analysis showed mRNA in the normal size-range, and immunocytochemistry on individual lymphocytes indicated that FMRP, the protein product of FMR1, was present. In conclusion, it is unlikely that FMR1 plays a role in the phenotype of this patient. Other genes may be responsible for the combination of mental retardation and macroorchidism. 26 refs., 4 fig., 1 tab.

• OSTI ID: 478899
• Journal Information: American Journal of Medical Genetics, Vol. 64, Issue 2; Other Information: PBD: 9 Aug 1996
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
MENTAL DISORDERS
GENETICS
MALES
HEREDITARY DISEASES
PHENOTYPE
CONGENITAL MALFORMATIONS
GENES
GENE MUTATIONS
GENETIC MAPPING
GENE REGULATION
TRANSCRIPTION
STRUCTURE-ACTIVITY RELATIONSHIPS
HUMAN X CHROMOSOME
NUCLEOTIDES
PROTEINS
AMINO ACIDS
DNA-CLONING
DNA SEQUENCING
BIOLOGICAL MARKERS
POLYMERASE CHAIN REACTION