A study of two Chinese patients with tetrasomy and pentasomy 15q11q13 including Prader-Willi/Angelman syndrome critical region present with developmental delays and mental impairment

Abstract

BackgroundThe proximal chromosome 15q is prone to unequal crossover, leading to rearrangements. Although 15q11q13 duplications are common in patients with developmental delays and mental impairment, 15q aneusomies resulting in greater or equal to 4 copies of 15q11q13 are rare and no pentasomy 15q11q13 has been reported in the literature. Thus far, all reported high copy number 15q11q13 cases are from the West populations and no such study in Chinese patients have been documented. Dosage-response pattern of high copy number 15q11q13 on clinical presentations is still a subject for further study.Case PresentationIn this study, we characterized two Han Chinese patients with high copy number 15q11q13. Using chromosome banding, high resolution SNP-based cytogenomic array, Fluorescence in situ hybridization, and PCR-based microsatellite analysis, we identified two patients with tetrasomy 15q11q13 and pentasomy 15q11q13. Both 15q11q13 aneusomies resulted from a maternally inherited supernumerary marker chromosome 15, and each was composed of two different sized 15q11q13 segments covering the Prader-Willi/Angelman critical region: one being about 10 Mb with breakpoints at BP1 and BP5 regions on 15q11 and 15q13, respectively, and another about 8 Mb in size with breakpoints at BP1 and BP4 regions on 15q. Both patients presented with similar clinical features that included neurodevelopmental delays, mental impairment, speech and autistic behavior, and mild dysmorphism. The patient with pentasomy 15q11q13 was more severely affected than the patient with tetrasomy 15q11q13. Low birth weight was noted in patient with pentasomy 15q1q13.ConclusionsTo the best of our knowledge, this is the first case of pentasomy 15q11q13 and the first study of high copy number 15q11q13 in Han Chinese patients. Our findings demonstrate that patients with tetrasomy and pentasomy of chromosome 15q11q13 share similar spectrum of phenotypes reported in other high copy number 15q11q13 patients in the West, and positive correlation between 15q11q13 copy number and degree of severity of clinical phenotypes. Low birth weight observed in the pentasomy 15q11q13 patient was not reported in other patients with high copy number 15q11q13. Additional studies would be necessary to further characterize high copy number 15q11q13 aneusomies.

Growth patterns of Chinese patients with Prader‐Willi syndrome

“…The analysis is based on 33 patients investigated in Peking Union Medical College Hospital from 1994 to 2014 (male 18, female 15, aged 5 months to 18 years) and 87 cases with reported PWS from other tertiary hospitals in Mainland China (male 55, female 32, aged 8 days to 18 years). We retrospectively obtained the recorded growth parameters (length/height and weight) from charts of our patients or retrieved from Pubmed Fong et al 2012;Ma et al 2012;Yang et al 2013;Yu et al 2013;Zhu et al 2013;Lu et al 2014a) (http://www.ncbi.nlm.nih.gov/pubmed) and China National Knowledge Infrastructure (http://www.cnki.net). In all patients considered for this study, the diagnosis was either confirmed by stringent clinical diagnostic criteria (Holm et al 1993) or by genetic investigation (n = 39; 32.5%).…”

Marker chromosome containing genes of rRNA related to intellectual disability: case report

“…В нем часто формируются точки разрыва с последующим формированием маркерных хромосом, что приводит к тетрасомии 15p и частично 15q. Клиническая и цитогенетическая картина, характерная для этого пациента, соответствует синдрому дупликации 15q11-q13, который зачастую сопровождается синдромами Прадера-Вилли или Ангельмана, так как затронут критический район для этих синдромов [6][7][8][9]. Особо следует отметить увеличение копийности генов рРНК, при котором на маркерной хромосоме экспрессируются дополнительные копии, что также может вносить вклад в развитие клинической картины.…”

Small supernumerary marker chromosome 15 and a ring chromosome 15 associated with a 15q26.3 deletion excluding the IGF1R gene

“…This abnormality frequently occurs as a random event during meiosis. Maternal inheritance of the duplicated chromosomal region often leads to developmental problems (Battaglia, ; Yang et al, ). Increased or decreased body size, learning disabilities, renal abnormalities and a typical facial morphology including long, thin face, prominent chin and nose are also observed in patients with 15q duplication syndrome (Battaglia, ; Urraca et al, ).…”