Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy
Background and objectives: Dilated cardiomyopathy (DCM) is a rare cardiac disease characterised by left ventricular enlargement, reduced left ventricular contractility, and impaired systolic function. Childhood DCM is clinically and genetically heterogenous and associated with mutations in over 100...
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doaj-90f33cff3fa34d90bac90b73fd2ac6062020-11-25T00:43:11ZengMDPI AGMedicina1010-660X2019-01-015511710.3390/medicina55010017medicina55010017Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated CardiomyopathyAtiyeh M Abdallah0S. Justin Carlus1Abdulhadi H Al-Mazroea2Mohammad Alluqmani3Yousef Almohammadi4Zahurul A Bhuiyan5Khalid M Al-Harbi6West Midlands Regional Genetics Laboratory, The Birmingham Women’s and Children’s NHS Foundation Trus, B15 2TT Birmingham, UKCardiogenetics Unit, Pediatrics Department, College of Medicine, Taibah University, 30001 Al-Madinah, Saudi ArabiaCardiogenetics Unit, Pediatrics Department, College of Medicine, Taibah University, 30001 Al-Madinah, Saudi ArabiaCardiogenetics Unit, Pediatrics Department, College of Medicine, Taibah University, 30001 Al-Madinah, Saudi ArabiaSecurity Forces Medical Centre, 30010 Al-Madinah, Saudi ArabiaUnit of Cardiogenetics Research, Division of Genetic Medicine, BT.02. 251, Beaumont 29, 1011 Lausanne, SwitzerlandCardiogenetics Unit, Pediatrics Department, College of Medicine, Taibah University, 30001 Al-Madinah, Saudi ArabiaBackground and objectives: Dilated cardiomyopathy (DCM) is a rare cardiac disease characterised by left ventricular enlargement, reduced left ventricular contractility, and impaired systolic function. Childhood DCM is clinically and genetically heterogenous and associated with mutations in over 100 genes. The aim of this study was to identify novel variations associated with infantile DCM. Materials and Methods: Targeted next generation sequencing (NGS) of 181 cardiomyopathy-related genes was performed in three unrelated consanguineous families from Saudi Arabia. Variants were confirmed and their frequency established in 50 known DCM cases and 80 clinically annotated healthy controls. Results: The three index cases presented between 7 and 10 months of age with severe DCM. In Family A, there was digenic inheritance of two heterozygous variants: a novel variant in LAMA4 (c.3925G > A, p.Asp1309Asn) and a known DCM mutation in MYH7 (c.2770G > A; p.Glu924Lys). The LAMA4 p.Asp1309Asn variant was predicted to be likely pathogenic according to international guidelines. The other two families had no identifiable potentially deleterious variants. Conclusions: Inheritance of two genetic variants may have a synergistic or dose effect to cause severe DCM. We report of a novel p.Asp1309Asn variation associated with DCM. Targeted NGS is useful in the molecular diagnosis of DCM and to guide whole-family management and counselling.http://www.mdpi.com/1010-660X/55/1/17targeted gene sequencingdilated cardiomyopathydigenicMYH7LAMA4Saudi Arabia |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Atiyeh M Abdallah S. Justin Carlus Abdulhadi H Al-Mazroea Mohammad Alluqmani Yousef Almohammadi Zahurul A Bhuiyan Khalid M Al-Harbi |
| spellingShingle |
Atiyeh M Abdallah S. Justin Carlus Abdulhadi H Al-Mazroea Mohammad Alluqmani Yousef Almohammadi Zahurul A Bhuiyan Khalid M Al-Harbi Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy Medicina targeted gene sequencing dilated cardiomyopathy digenic MYH7 LAMA4 Saudi Arabia |
| author_facet |
Atiyeh M Abdallah S. Justin Carlus Abdulhadi H Al-Mazroea Mohammad Alluqmani Yousef Almohammadi Zahurul A Bhuiyan Khalid M Al-Harbi |
| author_sort |
Atiyeh M Abdallah |
| title |
Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy |
| title_short |
Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy |
| title_full |
Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy |
| title_fullStr |
Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy |
| title_full_unstemmed |
Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy |
| title_sort |
digenic inheritance of lama4 and myh7 mutations in patient with infantile dilated cardiomyopathy |
| publisher |
MDPI AG |
| series |
Medicina |
| issn |
1010-660X |
| publishDate |
2019-01-01 |
| description |
Background and objectives: Dilated cardiomyopathy (DCM) is a rare cardiac disease characterised by left ventricular enlargement, reduced left ventricular contractility, and impaired systolic function. Childhood DCM is clinically and genetically heterogenous and associated with mutations in over 100 genes. The aim of this study was to identify novel variations associated with infantile DCM. Materials and Methods: Targeted next generation sequencing (NGS) of 181 cardiomyopathy-related genes was performed in three unrelated consanguineous families from Saudi Arabia. Variants were confirmed and their frequency established in 50 known DCM cases and 80 clinically annotated healthy controls. Results: The three index cases presented between 7 and 10 months of age with severe DCM. In Family A, there was digenic inheritance of two heterozygous variants: a novel variant in LAMA4 (c.3925G > A, p.Asp1309Asn) and a known DCM mutation in MYH7 (c.2770G > A; p.Glu924Lys). The LAMA4 p.Asp1309Asn variant was predicted to be likely pathogenic according to international guidelines. The other two families had no identifiable potentially deleterious variants. Conclusions: Inheritance of two genetic variants may have a synergistic or dose effect to cause severe DCM. We report of a novel p.Asp1309Asn variation associated with DCM. Targeted NGS is useful in the molecular diagnosis of DCM and to guide whole-family management and counselling. |
| topic |
targeted gene sequencing dilated cardiomyopathy digenic MYH7 LAMA4 Saudi Arabia |
| url |
http://www.mdpi.com/1010-660X/55/1/17 |
| work_keys_str_mv |
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