335.4 kb microduplication in chromosome band Xp11.2p11.3 associated with developmental delay, growth retardation, autistic disorder and dysmorphic features.
About 10% of causative mutations for mental retardation in male patients involve X chromosome (X-linked mental retardation, XLMR). We describe a case of a 3-year-old boy presenting with developmental delay, autistic features and growth and speech delay. Array-CGH analysis detected a microduplication on the X chromosome (Xp11.2p11.3), spanning 335.4 kb and including 3 known genes (ZNF81, ZNF182 and SPACA5). Genome-wide association studies show that approximately 30% of mutations causing XLMR are located in Xp11.2p11.3, where few pathogenic genes have been identified to date (such as ZNF41, PQB1 and ZNF81). ZNF81 codifies a zinc finger protein and mutations (non-sense mutations, deletions and structural rearrangements) involving this gene have already been described in association with mental retardation. Larger duplications in the same region have also been observed in association with mental retardation, and, in one case, the over-expression of ZNF81 has also been verified by mRNA quantification. No duplications of the single gene have been identified. To our knowledge, the microduplication found in our patient is the smallest ever described in Xp11.2p11.3. This suggests that the over-expression of ZNF81 could have pathological effects.
S. Pietro Fatebenefratelli Hospital, UOSD Medical Genetics, Rome, Italy.
Viola
V
Alesi
Marta
M
Bertoli
Giuseppe
G
Barrano
Barbara
B
Torres
Silvia
S
Pusceddu
Myriam
M
Pastorino
Chiara
C
Perria
Anna Maria
AM
Nardone
Antonio
A
Novelli
Gigliola
G
Serra
D001321:Autistic Disorder / Q000235:genetics*; D002675:Child, Preschool; D058674:Chromosome Duplication / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D006801:Humans; D007519:Isoantigens / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D029589:Seminal Plasma Proteins / Q000235:genetics; D012729:Sex Chromosome Aberrations
D007519:Isoantigens; D051741:Kruppel-Like Transcription Factors; C575494:SPACA5 protein, human; D029589:Seminal Plasma Proteins; C089460:ZNF81 protein, human