Next-Generation Sequencing in Unexplained Intellectual Disability

被引：2

作者：

Sandal, Sapna ^{[1
]}

Verma, Ishwar Chander ^{[1
]}

Mahay, Sunita Bijarnia ^{[1
]}

Dubey, Sudhisha ^{[1
]}

Sabharwal, R. K. ^{[2
]}

Kulshrestha, Samarth ^{[1
]}

Saxena, Renu ^{[1
]}

Suman, Praveen ^{[3
]}

Kumar, Praveen ^{[2
]}

Puri, Ratna Dua ^{[1
]}

机构：

[1] Sir Ganga Ram Hosp, Inst Med Genet & Genom, New Delhi, India

[2] Sir Ganga Ram Hosp, Dept Pediat Neurol, New Delhi, India

[3] Sir Ganga Ram Hosp, Dept Dev Pediat, New Delhi, India

来源：

INDIAN JOURNAL OF PEDIATRICS | 2024年 / 91卷 / 07期

关键词：

Intellectual disability; Developmental delay; Next generation sequencing; Autosomal recessive intellectual disability; GUIDELINES; DIAGNOSIS;

D O I：

10.1007/s12098-023-04820-5

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

ObjectivesTo determine the diagnostic yield of next generation sequencing (NGS) in patients with moderate/severe/profound intellectual disability (ID) unexplained by conventional tests and to assess the impact of definitive diagnosis on the clinical management and genetic counselling of these families.MethodsThis was a ambi-directional study conducted at Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi. The study comprised 227 patients (prospective cohort - 126, retrospective cohort - 101) in whom NGS based tests were performed.ResultsThe mean age of study cohort was 4.5 +/- 4.4 y (2.5 mo to 37.3 y). The male: female ratio was 1.6:1. The overall diagnostic yield of NGS was 53.3% (121/227) with causative variants identified in 84 known ID genes. Autosomal recessive intellectual disability (ARID) (23.3%, 53/227) was the most common followed by autosomal dominant intellectual disability (ADID) (20.7%, 47/227) and X-linked intellectual disability (XLID) (9.2%, 21/227). The diagnostic yield was notably higher for ID plus associated condition group (55.6% vs. 20%) (p = 0.0075, Fisher's exact test) compared to isolated ID group. The impact of diagnosis on active or long-term management was observed in 17/121 (14%) and on reproductive outcomes in 26/121 (21.4%) families.ConclusionsThere is paucity of data on molecular genetic spectrum of ID from India. The current study identifies extensive genetic heterogeneity and the impact of NGS in patients with ID unexplained by standard genetic tests. The study identified ARID as the most common cause of ID with additional implications for reproductive outcomes. It reiterates the importance of phenotype in genetic testing.

引用

页码：682 / 695

页数：14

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