Characterization of a Complex Chromosomal Rearrangement Involving a de novo Duplication of 9p and 9q and a Deletion of 9q

Abstract

Rearrangements of the distal region of 9p are important chromosome imbalances in human beings. Trisomy 9p is the fourth most frequent chromosome anomaly and is a clinically recognizable syndrome. Kleefstra syndrome, previously named 9q subtelomeric deletion syndrome, is either caused by a submicroscopic deletion in 9q34.3 or an intragenic mutation of EHMT1. We report a Mexican male patient with abnormal development, dysmorphism, systemic anomalies and a complex chromosomal rearrangement (CCR). GTG-banding revealed a 46,XY,add(9)(q34.3) karyotype, whereas array analysis resulted in arr[hg19] 9p24.3p23(203,861-11,842,172)×3, 9q34.3(138,959,881-139,753,294)×3, 9q34.3(139,784,913-141,020,389)×1. Array and karyotype analyses were normal in both parents. Partial duplication of 9p is one of the most commonly detected autosomal structural abnormalities in liveborn infants. A microdeletion in 9q34.3 corresponds to Kleefstra syndrome, whereas a microduplication in 9q34.3 shows a great clinical variability. Here, we present a CCR in a patient with multiple congenital anomalies who represents the first case with partial 9p trisomy, partial 9q trisomy and partial 9q monosomy.

Prenatal diagnosis of maternal partial trisomy 9p23p24.3 and 14q11.2q21.3 in a fetus: a case report

“…In the present study, the fetus with 9p24.3p23 contained 32 OMIM pathological genes, including GLIS3 and SMARCA2. The GLIS3 gene partially had the same chromosome segments as described in the aforementioned 3-year-old boy [36]. The fetus might be prone to neonatal diabetes complicated with congenital hypothyroidism, and have intrauterine developmental retardation during pregnancy and low-set ears and craniosynostosis after birth.…”

“…Patients with 9p trisomy display variable degrees of mental retardation and head and facial abnormal features, such as microcephaly with a large anterior fontanelle, micrognathia, a prominent or bulbous nose, malformed protruding ears, deep-set eyes, mild down slanting of the palpebral fissures, downturned corners of the mouth, congenital heart defects, mental retardation, and kidney and skeletal anomalies [13,34]. A 3-year-old boy with de novo 9p24.2 to 9p23 was diagnosed with development lag and craniofacial anomalies [36]. Some studies reported that the partial duplication of 9p24.3p23 was related to microcephaly, autism, and other clinical phenotype-related diseases [4,15,37].…”

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.…”

“…2,9 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. 1 En menor frecuencia, pueden ocurrir anomalías en el sistema nervioso central, 2,4,6,7 cardiopatías congénitas y alteraciones renales. 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.…”

“…1 En menor frecuencia, pueden ocurrir anomalías en el sistema nervioso central, 2,4,6,7 cardiopatías congénitas y alteraciones renales. 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.…”