We report a patient with microcephalic primordial dwarfism with predominant Meier–Gorlin syndrome phenotype with ichthyosis and disabling multiple joint deformities in addition to classic features of the syndrome. The patient was a 10.5‐year‐old girl referred in view of short stature, joint deformities, and facial dysmorphism. There was history of intrauterine growth restriction and collodion like skin abnormality at birth. She had normal developmental milestones and intellect. On clinical evaluation, anthropometry was suggestive of proportionate short stature and microcephaly. There was abnormal posture due to spine and peripheral joint deformities, along with ichthyosis, facial, and digital dysmorphism. Skeletal radiographs showed radial subluxation, acetabular dysplasia and hip dislocation, bilateral knee joint dislocation, absent patellae, slender long bones with delayed bone age, and subluxation of small joints of hands and feet. Work up for metabolic bone disease and peripheral blood karyotype was normal. Whole exome sequencing revealed a pathogenic homozygous variant c.C1297T (p.Pro433Ser) in the exon 8 of DONSON gene. This report further expands the genotypic–phenotypic spectrum of the group of disorders known as Cell Cycle‐opathies.
AbstractMultiplex ligation-dependent probe amplification (MLPA) detects exonic deletions and duplications in the DMD gene in around 65 to 70% of patients with the Duchenne muscular dystrophy (DMD) phenotype. This study looks at the diagnostic yield of next-generation sequencing (NGS) and the mutation spectrum in an Asian Indian cohort of MLPA-negative cases with the DMD phenotype. NGS-based sequencing of DMD gene was done in 28 MLPA-negative cases (25 male probands with the DMD phenotype and 3 obligate carrier mothers of deceased affected male patients) and disease-causing variants were identified in 19 (67.9%) of these cases. Further molecular testing in four of the remaining nine cases revealed gene variants associated with limb girdle muscular dystrophies. Thus, NGS-based multigene panel testing for muscular dystrophy-associated genes or clinical exome sequencing rather than targeted DMD gene sequencing appears to be a more cost-effective testing modality with better diagnostic yield, for MLPA-negative patients with the DMD phenotype.
We report a newborn born to a consanguineous couple with antenatally detected dilatation of third ventricle, unilateral talipes, and intra uterine growth retardation. On examination, there was facial dysmorphism, hypotonia, encephalopathy, joint laxity and muscle hypertrophy in addition to left foot talipes. On evaluation, there were renal cortical cysts, rhizomelia, chondrodysplasia punctata and elevated muscle enzymes, along with a dilated third ventricle. As the phenotype was not consistent with any of the muscular dystrophies or the peroxisomal disorders, an exome sequencing was requested. It revealed a combination of Zellweger syndrome and Ullrich congenital muscular dystrophy type 1.
This is report of a case of
RET
associated Hirschsprung disease in a fetus diagnosed using exome sequencing. The fetus initially presented with echogenic bowel at 16 weeks with maternal first trimester serum screen showing increased risk for Trisomy 21. Amniotic fluid karyotype, ΔF508
CFTR
genotype and maternal TORCH serology were normal. Subsequent ultrasonograms showed dilated bowel loops, predominantly large bowel. Following delivery at 24 weeks, a post-mortem examination was performed. Dilated bowel was confirmed with no structural gut abnormality and no other dysmorphic finding. Histopathology revealed agangliosis confirming a diagnosis of Hirschsprung disease. Exome sequencing done on fetal DNA from amniotic fluid revealed a putative pathogenic heterozygous c.1438G > A variant in exon 7 of
RET
gene, which was inherited from the asymptomatic mother. This enabled genetic counseling and prenatal diagnosis in subsequent pregnancy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.