Molecular genetic analysis of partial 9p trisomy in two Chinese families with mental retardation and facial anomaly

Abstract

Mental retardation is defined by significant limitations in intellectual function and adaptive behavior that occur before 18 years of age. Many chromosomal diseases come with mental retardation. We reported two Chinese families with partial trisomy 9p and other chromosome partial monosomy, clinical features of mental retardation and mild facial and pinkie anomalies. In the family 1, we showed that the proband carried a trisomy 9p21.3→pter and monosomy 21q22.3→qter by using fluorescence in situ hybridization analysis. Molecular genetic analysis defined the precise breakpoint on chromosome 9p between markers D9S1846 and D9S171, an interval of about 2.9 Mb on 9p21.3, and the breakpoint on chromosome 21q between markers D21S1897 and D21S1446, a region of about 1.5 Mb on 21q22.3. In the family 2, a patient with trisomy 9p21.3→pter and monosomy 5p15.33→pter, and a de novo maternal balanced translocation between chromosomes 5 and 9 was identified in his mother. Cytogenetic and molecular genetic analysis defined the precise breakpoints on chromosome 9p21.3 and chromosome 5p15.33. Further clinical investigation found that any individual had no refractoriness eczema disease except the proband in this family. These results further implicate that trisomy 9p is associated with mental retardation, and that there may be key gene duplication on chromosome 9p21.3→9pter responsible for mental retardation and mild facial anomaly. This result has been applied successfully in prenatal diagnosis of the second family.

Trisomy 9p. A brief clinical, diagnostic and therapeutic description

“…In most cases, partial trisomy 9p occurs as a result of parental reciprocal translocation between chromosome 9 and other autosome. 2,3,8 Therefore, phenotypic heterogeneity is correlated to the variable size of the duplicated segment (producing trisomy 9p) and the monosomy of the other chromosomal segment. 3,4,8 To a lower extent, it is the result of a spontaneous (de novo) genetic alteration occurring for unknown reasons during early embryonic development, i.e., it is not passed by any of the parents.…”

“…2,3,8 Therefore, phenotypic heterogeneity is correlated to the variable size of the duplicated segment (producing trisomy 9p) and the monosomy of the other chromosomal segment. 3,4,8 To a lower extent, it is the result of a spontaneous (de novo) genetic alteration occurring for unknown reasons during early embryonic development, i.e., it is not passed by any of the parents. 2,8 Based on the aforementioned information, e s t a b l i s h i n g t h e g e n o t y p e -p h e n o t y p e correlation may be hindered by the presence of small deletions or duplications affecting other chromosomes in most reported cases of trisomy 9p.…”

“…3,4,8 To a lower extent, it is the result of a spontaneous (de novo) genetic alteration occurring for unknown reasons during early embryonic development, i.e., it is not passed by any of the parents. 2,8 Based on the aforementioned information, e s t a b l i s h i n g t h e g e n o t y p e -p h e n o t y p e correlation may be hindered by the presence of small deletions or duplications affecting other chromosomes in most reported cases of trisomy 9p. 2,10 Such additional genetic alterations make it difficult to understand which abnormalities have been caused by trisomy 9p or by other chromosomal changes.…”

Trisomía 9p. Una breve descripción clínica, diagnóstica y terapéutica

“…S e d i s t i n g u e p o r p r e s e n t a r retraso del crecimiento, psicomotor y m e n t a l . E n t r e l a s d i s m o r f i a s cráneo-faciales, pueden exhibir microbraquicefalia, [1][2][3][4]7 fontanela a n t e r i o r a m p l i a , 2 , 7 h e n d i d u r a s palpebrales hundidas, hacia abajo y afuera, [1][2][3]7 hipertelorismo, 1,2,3,8 raíz nasal prominente, punta nasal bulbosa, 1,3,7,9 filtrum corto, 3 comisuras labiales hacia abajo, 1,7-9 micrognatia, 2,7 pabellones auriculares de implantación baja, 1,3 protuberantes y malformados. 2,9 El cuello puede ser corto y ancho, 3 se puede evidenciar cifoescoliosis, 2 lordosis, 2,6 talla baja, [3][4][5] de inicio pre-o posnatal, 5 con frecuencia, asociado al retraso en la edad ósea, 1,2,5 anomalías en las extremidades caracterizada por dedos cortos, 1,10 clinodactilia d e l q u i n t o d e d o , 9 u ñ a s d e l o s dedos de los pies hipoplásicas.…”

“…2,4,6,7 Algunos estudios mostraron una asociación con hepatoblastoma, 7,9,11 carcinoma hepatocelular, 11,12 convulsiones, comportamiento autolesivo, 8 disfagia, 9 lupus eritematoso y presencia de queloides. 8 En la Tabla 1, [1][2][3][4]6,13 se muestran los hallazgos clínicos que pueden evidenciarse en la trisomía 9p con sus respectivas frecuencias.…”