P16.8 Clinical and genetic findings in an unusual pedigree with infantile spinal muscular atrophy caused by a compound heterozygous mutation in the SMN1 gene

The authors report a child with spinal muscular atrophy with respiratory distress type 1 (SMARD1). She presented atypically with hypothyroidism and heart failure due to septal defects that required early heart surgery and microcephaly in association with cerebral atrophy and thin corpus collosum. The subsequent asymmetrical onset of diaphragmatic paralysis, persistent hypotonia, and generalized muscle weakness led to the suspicion of spinal muscular atrophy with respiratory distress type 1. Sanger sequencing confirmed a compound heterozygous mutation in the Immunoglobulin Mu Binding Protein 2 (IGHMBP2) gene, with a known mutation c.2362C > T (p.Arg788*) and a novel frameshift mutation c.2048delG (p.Gly683A1afs*50). Serial nerve conduction study and electromyography confirmed progressive sensorimotor polyneuropathy and neuronopathy. In summary, this case report describes a child with spinal muscular atrophy with respiratory distress type 1 also with congenital cardiac disease and endocrine dysfunction, expanding the phenotypic spectrum of this condition. A high index of suspicion is needed in diagnosing this rare condition to guide the management and genetic counseling.

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Whole blood gene expression analysis in idiopathic infantile hypercalcemia due to compound heterozygous mutation in theCYP24A1gene in an Austrian 4-month-old boy and his family

Bone Abstracts ◽

10.1530/boneabs.4.p163 ◽

2015 ◽

Author(s):

Daniela Hofer ◽

Verena Zachhuber ◽

Lisa Lindheim ◽

Julia Munzker ◽

Olivia Trummer ◽

...

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Whole Blood ◽

Gene Expression Analysis ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Blood Gene Expression ◽

Idiopathic Infantile Hypercalcemia

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Novel compound heterozygous mutation in ASXL3 causing bainbridge-ropers syndrome and primary IGF1 deficiency: Expanding phenotype

Endocrine Abstracts ◽

10.1530/endoabs.45.p65 ◽

2016 ◽

Author(s):

Dinesh Giri ◽

Astrid Weber ◽

Mohammed Didi ◽

Matthew Peak ◽

Paul McNamara ◽

...

Keyword(s):

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Igf1 Deficiency

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Orphan designation: adeno-associated viral vector serotype hu68 containing the human SMN1 gene, Treatment of spinal muscular atrophy

Case Medical Research ◽

10.31525/cmr-6939f8 ◽

2018 ◽

Author(s):

Keyword(s):

Spinal Muscular Atrophy ◽

Viral Vector ◽

Muscular Atrophy ◽

Smn1 Gene ◽

Orphan Designation ◽

Gene Treatment

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Orphan designation: adeno-associated viral vector serotype hu68 containing the human SMN1 gene, Treatment of spinal muscular atrophy

Case Medical Research ◽

10.31525/cmr-6ac6fc ◽

2019 ◽

Author(s):

Keyword(s):

Spinal Muscular Atrophy ◽

Viral Vector ◽

Muscular Atrophy ◽

Smn1 Gene ◽

Orphan Designation ◽

Gene Treatment

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A Novel Compound Heterozygous Mutation in ABCB4 Gene Leading to Cholelithiasis, Progressive Familial Intrahepatic Cholestasis (Type 3), and Cirrhosis in a Child

Journal of Child Science ◽

10.1055/s-0040-1717106 ◽

2020 ◽

Vol 10 (01) ◽

pp. e134-e136

Author(s):

Nida Mirza ◽

Smita Malhotra ◽

Anupam Sibal

Keyword(s):

Intrahepatic Cholestasis ◽

Gall Stone ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Initial Symptom ◽

Progressive Familial Intrahepatic Cholestasis ◽

Presenting Symptoms ◽

Abcb4 Gene ◽

Type 3

AbstractProgressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive disorders of childhood which presents with intermittent or progressive episodes of cholestasis, with jaundice and pruritus as most common presenting symptoms. PFIC type 3 occurs due to mutations in the ABCB4 gene, mutation in this gene has wide spectrum of features which include intrahepatic stones, cholelithiasis, PFIC type 3, and intrahepatic cholestasis of pregnancy. Here, we are reporting a peculiar case of young male adolescent with novel variant compound heterozygote missense mutation in ABCB4 gene who had gall stone as initial symptom, followed by symptoms of PFIC and eventually decompensated chronic liver disease.

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Leptin Receptor Compound Heterozygosity in Humans and Animal Models

International Journal of Molecular Sciences ◽

10.3390/ijms22094475 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4475

Author(s):

Claudia Berger ◽

Nora Klöting

Keyword(s):

Food Intake ◽

Animal Models ◽

Leptin Receptor ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Compound Heterozygosity ◽

Therapy Options ◽

Obese Phenotype ◽

Deficient Mice

Leptin and its receptor are essential for regulating food intake, energy expenditure, glucose homeostasis and fertility. Mutations within leptin or the leptin receptor cause early-onset obesity and hyperphagia, as described in human and animal models. The effect of both heterozygous and homozygous variants is much more investigated than compound heterozygous ones. Recently, we discovered a spontaneous compound heterozygous mutation within the leptin receptor, resulting in a considerably more obese phenotype than described for the homozygous leptin receptor deficient mice. Accordingly, we focus on compound heterozygous mutations of the leptin receptor and their effects on health, as well as possible therapy options in human and animal models in this review.

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