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Multi-omics approach identifies a novel recessive pathogenic variant in the TNNT3 gene in two siblings with congenital myopathy.

TNNT3 is the fast skeletal muscle troponin T compound of the troponin complex. Dominantly inherited pathogenic missense variants in TNNT3 ca … rable disease course in some patients, although with an overall milder disease presentation in both siblings. It also highlights the utility of a combined multi-omics approach to diagnose previously unsolved cases of congenital myopathy.

Clinical efficacy of elexacaftor-tezacaftor-ivacaftor in two siblings with homozygous I1234V mutation cystic fibrosis: A prospective case series.

BACKGROUND: The missense CFTR variant I1234V (c.3700A > G) produces class II protein-folding defects and is prevalent in the Middle East, yet clinical evidence for elexacaftor/tezacaftor/ivacaftor (ETI) in homozygous carriers is sparse. We prospectively evaluated ETI efficacy and safety in two paediatric siblings with homozygous I1234V cystic fibrosis (CF). METHODS: A single-centre, prospective case series was undertaken at King Fahad Medical City. Baseline assessments included spirometry, body-mass index (BMI), sputum microbiology, liver biochemistry and high-resolution chest CT. ETI was ini…

Novel compound heterozygous CYP17A1 mutations identified in a family with two siblings affected by 17α-hydroxylase/17,20-lyase deficiency.

BACKGROUND: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH), caused by mutations in th … is study examined the clinical features, biochemical profiles, and genetic background of two 46, XY siblings from the same family, both diagnosed with 17OHD-a scenario that is uncommonly seen in clinical practice. We performed a genetic analysis of the CYP17A1 gene in two generations of the family to confirm the diagnosis. RESULTS: Both patients are pheno …

Three Siblings Born to the Same Mother with Varying Degrees of Strong Positivity for Blocking Type TSH Receptor Antibodies.

A hypothyroid mother, due to thyroid stimulation-blocking antibody (TSBAb), gave birth three times. Although her TSBAb levels remained almost 100%, her thyrotropin receptor antibody (TRAb) levels before delivery varied as follows: 315.0, 88.2 and 34.9 IU/L in the first, second, and third pregnancies, respectively. The first baby had a hypoplastic thyroid gland and developed severe hypothyroidism three days after birth. The second and third babies only showed latent hypothyroidism. Apparent neonatal hypothyroidism due to maternal TSBAb occurs when TRAb levels are very high, and extremely high T

Clinically discordant siblings with spinal muscular atrophy: insights from their patient-specific iPSC-derived motor neurons and literature review.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by homozygous loss of the SMN1 gene. Copy number of the nearly identical paralog, SMN2, correlates with disease severity. SMN2 is the primary modifier of SMA, with only a few other modifiers reported. We reviewed the literature of rare siblings affected by SMA that show discordance in clinical presentation despite having the same number of SMN2 copies, which predicts the presence of genetic modifiers. We further recruited a sibling pair with discordant clinical presentations and performed detailed characterization. We utilized…

Результаты двух братьев и сестер с запоздалой болезнью Краббе после пересадки стволовых клеток аллогенетической гематотипией: и обзор литературы.

ЦЕЛИ: Сопоставление запаздываемого заболевания Краббе (КД) и результатов между двумя братьями и сестрами в связи с трансплантацией стволовых клеток с использованием аллогенетических гематополиетических стволовых клеток (ХЦТ). Методика: Мы представляем описательный отчет о двух братьях и сестрах с поздним наступлением KD и об их клиническом курсе до и после HSCT. РЕЗУЛЬТАТЫ: Индексный случай с неврологическими симптомами, которые предположительно диагностировались с множественным склерозом (МС). Несмотря на лечение иммунной терапией, пациент продолжал постепенно снижаться, что вызывало переоцен

Совпадение в аннотации оригинала
OBJECTIVES: To compare delayed-onset Krabbe disease (KD) and outcomes between two siblings in relation to allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We provide a descriptive report on two siblings with late-onset KD and their clinical course before and after HSCT. RESULTS: The index case presented with neurological symptoms that we…

Case report: Identification of facioscapulohumeral muscular dystrophy 1 in two siblings with normal phenotypic parents using optical genome mapping.

OBJECTIVE: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is one of the most common forms of autosomal-dominant muscular dystrophies … d higher CpG6 methylation levels than that of her younger brother. CONCLUSIONS: In this study, two siblings with FSHD1 with phenotypically normal parents were identified by OGM. Our findings suggest that the 4qA allele of four D4Z4 repeats was inherited through maternal germline mosaicism. The clinical phenotype heterogeneity is influenced by the CpG6 met …

Siblings with vitamin D-dependent rickets type 1A: Importance of genetic testing and a review of genotype-phenotype correlations.

Vitamin D-dependent rickets type 1A (VDDR1A) is a rare condition caused by biallelic pathogenic variants in CYP27B1, which encodes 25-hydroxyvitamin D3-1-α-hydroxylase. Inadequate activity of this enzyme results in deficient 1α-hydroxylation of inactive 25-hydroxyvitamin D to biologically active 1,25-dihydroxyvitamin D, with consequent adverse effects on calcium and phosphate metabolism. A female child was clinically diagnosed at 18 months old with hypophosphatemic rickets based on phenotype and biochemical testing, with neither parent affected. A subsequent affected male sibling led to the re

Biallelic OTUD6B variants associated with a Kabuki syndrome-like disorder in three siblings: A clinical report and literature review.

Biallelic variants in the OTUD6B gene have been reported in the literature in association with an intellectual developmental disorder featuring dysmorphic facies, seizures, and distal limb abnormalities. Physical differences described for affected individuals suggest that the disorder may be clinically recognizable, but previous publications have reported an initial clinical suspicion for Kabuki syndrome (KS) in some affected individuals. Here, we report on three siblings with biallelic variants in OTUD6B co-segregating with neurodevelopmental delay, shared physical differences, and other clin…

Cancer risk in the siblings of individuals with major birth defects: a large Nordic population-based case-control study.

BACKGROUND: Individuals with major birth defects are at increased risk of developing cancer, indicating a common aetiology. However, whether the siblings of individuals with birth defects are also at an increased risk of cancer is unclear. METHODS: We used nationwide health registries in four Nordic countries and conducted a nested case-control study. We included 40 538 cancer cases (aged 0-46 years) and 481 945 population controls (matched by birth year and country), born between 1967 and 2014. The relative risk of cancer among individuals whose siblings had birth defects was computed with o…

Case report: A novel c.1842_1845dup mutation of ETFDH in two Chinese siblings with multiple acyl-CoA dehydrogenase deficiency.

This article reports the characterization of two siblings diagnosed with late-onset multiple Acyl-CoA dehydrogenase deficiency (MADD) caused by mutations in electron transfer flavoprotein(ETF)-ubiquinone oxidoreductase (ETF-QO) (ETFDH) gene. Whole exome sequencing (WES) was performed in the proband's pedigree. Clinical phenotypes of Proband 1 (acidosis, hypoglycemia, hypotonia, muscle weakness, vomiting, hypoglycemia, hepatomegaly, glutaric acidemia, and glutaric aciduria) were consistent with symptoms of MADD caused by the ETFDH mutation. However, Proband 2 presented with only a short stature…

Generation of two iPSC lines (UMi038-A & UMi039-A) from siblings bearing an Alzheimer's disease-associated variant in SORL1.

Alzheimer's disease (AD) is the leading cause of dementia among older adults. SORL1, a top AD risk gene, encodes an endocytic receptor involved amyloid precursor protein (APP) trafficking and processing. Rare loss-of-function SORL1 variants are a strong genetic determinant of AD, and protein-truncating mutations have been found to be causal. We derived iPSCs from two siblings affected with early-onset AD who carry a rare protein-truncating deletion in SORL1 (c.4293delC) (Kunkle et al., 2017). The iPSC lines were characterized for pluripotency, differentiation potential, and genomic stability. …

Using Communication Tools to Explore Young Siblings' Experiences of Having a Brother or Sister with Pediatric Palliative Care Needs.

Siblings of children with palliative care needs often suffer feelings of being neglected, and their needs for information and involvement are frequently unmet. This study aims to explore the experiences and feelings of siblings of children with palliative care needs, and to determine what is important to them. Nine siblings, aged 6-14 years, were interviewed using four different communication tools: See-Hear-Do pictures, including the empty body as a separate element, Bear cards, and words originating from previous sibling research. Data were analyzed using conventional content analysis. Five …

Posterior lumbar interbody fusion for dysplastic lumbar spondylolisthesis with high-grade slippage in two adolescent siblings: two case reports.

BACKGROUND: Lumbar spondylolisthesis is reported to present with a familiar pattern, with the dysplastic type of spondylolysis being minor but more hereditary than the isthmic type. Siblings presenting during adolescence with neurological symptoms owing to high-grade dysplastic-type spondylolisthesis are rare. CASE PRESENTATION: The older brother suffered from left leg pain and numbness and dysesthesia of the right posterior thigh and calf and could not walk without a crutch at the age of 15 years. He had canal stenosis with disc bulging and dysplastic bilateral facet joint at L5/S1. The L5 v…

Significant neuropsychiatric symptoms: three mucopolysaccharidosis type IIIB cases, two of whom were siblings with a novel NAGLU gene mutation.

Mucopolysaccharidosis (MPS) type IIIB patients present with marked neurodevelopmental and neuropsychiatric problems and not with typical MPS symptoms such as coarse facial features, organomegaly, or short body height, especially at the first presentation. We present three pediatric cases, two of which are sisters with novel NAGLU gene mutations, to emphasize that diagnosis of MPS type IIIB should be remembered in patients presenting with neurodevelopmental and neuropsychiatric problems such as delayed speech, autistic-like symptoms, severe behavioral and sleep problems, motor deterioration or

Vitamin D-Dependent Rickets Type 1A in Two Siblings with a Hypomorphic CYP27B1 Variant Frequent in the African Population.

Vitamin D-dependent type 1A rickets (VDDR-1A) is a rare autosomal recessive disease due to the inability to convert 25-hydroxyvitamin D [25(OH)D] to the active form 1.25-dihydroxyvitamin D [1.25(OH) 2 D] by the enzyme 25(OH)D-1α-hydroxylase leading to low or low-normal serum levels of [1.25(OH) 2 D]. We report two sisters with rickets in whom the diagnosis of VDDR-1A was a challenge. They had normal 1.25(OH)2D levels, which are unusual with this condition but may be explained by the identified genotype. Both have compound heterozygous for two, most likely, hypomorphic CYP27B1 alleles: the nove

Two novel mutations in the MCM8 gene shared by two Chinese siblings with primary ovarian insufficiency and short stature.

BACKGROUND: Minichromosome maintenance complex component 8 (MCM8) is responsible for homologous recombination and DNA double-strand breaks (DSBs) repair and is the cause of primary ovarian insufficiency (POI), which is seldom diagnosed in adolescents and children. METHODS: Whole-exome sequencing was performed in a 13-year-old girl, and Sanger sequencing was used to identify potentially pathogenic variants in her sister (aged 6 years and 7 months) and parents. To identify potential pathogenic mutations, DSBs were induced by mitomycin C (MMC), and the DNA repair capacity was evaluated by the hi

Case report: discovery of 2 gene variants for aromatic L-amino acid decarboxylase deficiency in 2 African American siblings.

BACKGROUND: Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder with heterogeneous phenotypic spectrum resulting from disease-causing variants in the dopa decarboxylase (DDC) gene. Consensus guidelines recommend dopamine agonists, monoamine oxidase inhibitors, and other symptomatic treatments, but most patients have an unrelenting disease course with no response to these therapies. CASE PRESENTATION: We describe 2 African American siblings with AADC deficiency and identify 2 DDC gene variants not previously associated with the disorder. The patients were evaluated…

Link between childhood trauma and psychotic-like experiences in non-affected siblings of schizophrenia patients: A case-control study.

AIM: Prior research has consistently demonstrated a relationship between childhood trauma (CT) exposure and an increased risk of developing psychotic-like experiences (PLE) and disorders. Studying the link between CT and PLE in non-clinical populations with or without genetic risk factors could help elucidate the etiopathogeny of psychotic disorders, by removing the effect of confounding variables related to psychotic-spectrum illnesses. METHOD: A total of 60 non-affected siblings of patients with schizophrenia and 75 controls (aged 18-35 years) participated in a cross-sectional survey. The P…