title: Familial mental retardation syndrome ATR-16 due to an inherited cryptic subtelomeric translocation, t(3;16)(q29;p13.3).
abstract: In the search for genetic causes of mental retardation, we have studied a five-generation family that includes 10 individuals in generations IV and V who are affected with mild-to-moderate mental retardation and mild, nonspecific dysmorphic features. The disease is inherited in a seemingly autosomal dominant fashion with reduced penetrance. The pedigree is unusual because of (1) its size and (2) the fact that individuals with the disease appear only in the last two generations, which is suggestive of anticipation. Standard clinical and laboratory screening protocols and extended cytogenetic analysis, including the use of high-resolution karyotyping and multiplex FISH (M-FISH), could not reveal the cause of the mental retardation. Therefore, a whole-genome scan was performed, by linkage analysis, with microsatellite markers. The phenotype was linked to chromosome 16p13.3, and, unexpectedly, a deletion of a part of 16pter was demonstrated in patients, similar to the deletion observed in patients with ATR-16 syndrome. Subsequent FISH analysis demonstrated that patients inherited a duplication of terminal 3q in addition to the deletion of 16p. FISH analysis of obligate carriers revealed that a balanced translocation between the terminal parts of 16p and 3q segregated in this family. This case reinforces the role of cryptic (cytogenetically invisible) subtelomeric translocations in mental retardation, which is estimated by others to be implicated in 5%-10% of cases.
authors.affiliation: Department of Medical Genetics, University of Munich, Munich.
authors.forename: E
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: E
authors.initials: E
authors.lastname: Reyniers
authors.forename: S
authors.initials: S
authors.lastname: Uhrig
authors.forename: A
authors.initials: A
authors.lastname: Golla
authors.forename: J
authors.initials: J
authors.lastname: Wauters
authors.forename: P
authors.initials: P
authors.lastname: Kroisel
authors.forename: P
authors.initials: P
authors.lastname: Bossuyt
authors.forename: I
authors.initials: I
authors.lastname: Rost
authors.forename: K
authors.initials: K
authors.lastname: Jedele
authors.forename: H
authors.initials: H
authors.lastname: Zierler
authors.forename: S
authors.initials: S
authors.lastname: Schwab
authors.forename: D
authors.initials: D
authors.lastname: Wildenauer
authors.forename: M R
authors.initials: MR
authors.lastname: Speicher
authors.forename: P J
authors.initials: PJ
authors.lastname: Willems
authors.forename: T
authors.initials: T
authors.lastname: Meitinger
authors.forename: R F
authors.initials: RF
authors.lastname: Kooy
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013577:Syndrome; D016615:Telomere; D014178:Translocation, Genetic / Q000235:genetics*