No abstract

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.