The first patient with tandem duplication of 6q14q16: Molecular and phenotypic characterization

Abstract

Duplications of the long arm of chromosome 6 have been previously reported in a limited number of patients; however, most reported duplications encompass regions of chromosome 6 distal to band q21. Duplications restricted to the proximal portion of 6q are rare. We report an 8-year-old male with a 16.4 megabase (Mb) tandem duplication of chromosome 6q14.1q16.1 (chr6:78950191-95395865; hg19) who exhibited dysmorphic facial features, seizures, global developmental delay, intellectual disability, autism spectrum disorder, sensorineural hearing loss, and immune deficiency. This patient refines and potentially expands the current, poorly-characterized phenotype associated with duplication of this proximal 6q region. We recommend a low threshold for a hearing evaluation beyond newborn screening and for pursuing an immune work-up in patients with similar 6q duplications. © 2016 Wiley Periodicals, Inc.

Prenatal detection of pure proximal 6q14.1 microduplication encompassing LCA5 gene

“…Currently, the genotype-phenotype correlation of proximal 6q duplications remains unclear for lacking of clinic data. [ 6 ] To better define the interpretations of 6q14.1 duplication, we summarized duplicated cases involving the 6q14.1 region (Table 2 , Fig. 1 ).…”

“…As shown in Table 2, growth/ mental retardation and dysmorphic facial features could be observed in 4 cases (No. [3][4][5][6]. Language retardation (No.…”

“…1). [1,6,7,[18][19][20] All duplications involving 6q14.1 varied in size, and were associated with different regions of proximal 6q, locating between 6q11 and 6q21. All cases were postnatally diagnosed and the age ranged from neonate to 14y, presenting different degrees of clinic manifestations.…”

“…Since the first trisomy 6q case was documented in 1969, more than 40 cases have been described in clinic [3,4] . As a well-defined syndrome, patients of 6q duplication usually presented distinct phenotypes, including mental/growth retardation, low birth weight, short stature, feeding difficulties, microcephaly, prominent forehead, short webbed neck, downslanting palpebral fissures, flat nasal bridge, micrognathia, joint contractures, hypertelorism, carp mouth, heart malformations, brain anomalies, hearing loss, club feet, abnormal genitourinary system and so on [5–7] …”

“…[3,4] As a well-defined syndrome, patients of 6q duplication usually presented distinct phenotypes, including mental/growth retardation, low birth weight, short stature, feeding difficulties, microcephaly, prominent forehead, short webbed neck, downslanting palpebral fissures, flat nasal bridge, micrognathia, joint contractures, hypertelorism, carp mouth, heart malformations, brain anomalies, hearing loss, club feet, abnormal genitourinary system and so on. [5][6][7] Most trisomy 6q cases resulted from the abnormal segregation of a parental balanced translocation, which would usually lead to chromosomal 6q terminal duplication accompanied by another chromosomal deletion. The co-existence of these 2 types of chromosomal anomalies, especially the monosomy of another chromosome, would usually make it complicated to establish a clear interpretation for the genotype-phenotype correlation of pure 6q duplication.…”