Molecular cytogenetic analysis of de novo dup(5)(q35.2q35.3) and review of the literature of pure partial trisomy 5q.
An 11-year-old girl presented with the phenotype of microcephaly, moderate mental retardation, motor retardation, short stature, strabismus, brachydactyly, and facial dysmorphism. She had undergone surgery for inguinal hernias. Detailed examinations of the heart and other internal organs revealed normal findings. Her karyotype was 46,XX,dup(5)(q35.2q35.3) de novo. Molecular cytogenetic analysis showed a paternally derived 5q35.2 --> q35.3 direct duplication and led to a correlation between the particular genotype and phenotype. This is the first description of a direct duplication of 5q35.2 --> q35.3. Our case represents the smallest distal duplication of chromosome 5q that is not associated with congenital heart defects. Our case also represents the smallest distal duplication of chromosome 5q that is associated with short stature and microcephaly. Mutations or deletions of the NSD1 gene, mapped to 5q35.2 --> q35.3, has been known to cause Sotos syndrome with cerebral gigantism, macrocephaly, advanced bone age and overgrowth. Our case provides evidence that the gene dosage effect of the NSD1 gene causes a reversed phenotype of microcephaly and short stature.
Chen
Chih-Ping
CP
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China. cpc_mmh@yahoo.com
Lin
Shuan-Pei
SP
Lin
Chyi-Chyang
CC
Chen
Yann-Jang
YJ
Chern
Schu-Rern
SR
Li
Yueh-Chun
YC
Hsieh
Lie-Jiau
LJ
Lee
Chen-Chi
CC
Pan
Chen-Wen
CW
Wang
Wayseen
W
D000015:Abnormalities, Multiple / Q000235:genetics*; D000782:Aneuploidy; D002648:Child; D002871:Chromosome Banding; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D008831:Microcephaly / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction