Three Japanese patients with 3p13 microdeletions involving FOXP1.

BACKGROUND: FOXP1 is known as the gene responsible for neurodevelopmental delay associated with language impairment. Broad clinical findings also include feeding difficulty, muscular hypotonia, and distinctive features. These findings are common between patients with loss-of-function mutations in FOXP1 and 3p13 microdeletion involving FOXP1. Thus, "FOXP1-related intellectual disability syndrome" is now recommended. METHODS: After obtaining informed consent, chromosomal microarray testing was performed for patients with unknown etiology. RESULTS: We identified three Japanese patients with 3p13 microdeletions involving FOXP1. One of the patients showed an additional 1q31.3q32.1 deletion as de novo, which was rather considered as a benign copy number variant. CONCLUSION: This is the first report of patients with 3p13 microdeletions from Japan. All patients showed growth delay, moderate to severe developmental delay, hearing loss, and distinctive facial features including prominent forehead and mid facial hypoplasia. In addition, "square shaped face" commonly observed in all three patients may be a characteristic finding undescribed previously. From the obtained findings, "FOXP1-related intellectual disability syndrome" was considered to be clinically recognizable.

Identification of sleep hypoventilation in young individuals with Becker muscular dystrophy: A pilot study.

AIM: To report on sleep hypercapnia in Becker muscular dystrophy (BMD) at earlier stages than ever recognized. SUBJECTS AND METHODS: This retrospective study examined nocturnal hypercapnia in six young Becker muscular dystrophy (BMD) patients with deletions of one or more exons of DMD gene. Clinical information, consecutive data on forced vital capacity (FVC%), forced expiratory volume in one second (FEV1%), peak expiratory flow (PEF%), peak cough flow (PCF), average PCO2 in all-night monitoring, and left ventricular ejection fraction (LVEF) were reviewed. RESULTS: In five BMD patients, including three who were still ambulant, nocturnal average PCO2 was elevated to >45 mmHg at 12-31 years of age. Noninvasive positive pressure ventilation was initiated in four patients. Gradual declines in FVC% and PEF% were evident in one BMD patient with exon 3-7 deletion, whereas these functions did not change in the remaining BMD patients. PCF, FEV1%, and LVEF were less informative for the assessment of respiratory function in this patient series. CONCLUSION: Sleep hypercapnia was present in certain BMD patients, which was unexpected from the routine pulmonary function tests. Individualized assessment of nocturnal PCO2, partly based on the deletion types, should be further explored in the clinical practice of BMD patients.

Surface electromyogram and muscle ultrasonography for detection of muscle fasciculations in pediatric peripheral neuropathy.

A 12-year-old girl presented with talipes equinus of both legs, attenuation of upper and lower limb tendon reflexes, thermal hyperalgesia, and reduction of vibratory sensation. On clinical examination, muscle twitches of fingers of both hands, as well as the abductor halluces and the dorsal interossei muscles of the right foot were observed. Nerve conduction velocity was significantly declined in the upper and lower extremities. Needle electromyography (EMG) was not performed; however, ultrasonography revealed repetitive, semi-regular muscle twitches lasting 0.2-0.4s, concomitant with muscle discharges on surface EMG in the right foot muscles. These findings were compatible with contraction fasciculation in muscles under chronic reinnervation. Nerve and muscle biopsies were suggestive of chronic motor, sensory, and autonomic neuropathy. This is the first case of pediatric peripheral neuropathy where muscle fasciculation was noninvasively identified by simultaneous surface EMG and ultrasonography.

Clinical Diagnosis of Mendelian Disorders Using a Comprehensive Gene-Targeted Panel Test for Next-Generation Sequencing.

BACKGROUND: Genetic diagnoses provide beneficial information to patients and families. However, traditional genetic diagnoses are often difficult even for experienced clinicians and require recognition of characteristic patterns of signs or symptoms to guide targeted genetic testing for the confirmation of diagnoses. Next-generation sequencing (NGS) is a powerful genetic diagnostic tool. However, whole-genome and whole-exome sequencing (WES) are expensive, and the interpretation of results is difficult. Hence, target gene capture sequencing of gene panels has recently been applied to genetic diagnoses. Herein, we demonstrate that targeted sequencing approaches using gene panel testing are highly efficient for the diagnosis of Mendelian disorders. METHODS: NGS using TruSight one gene panel was performed in 17 families and 20 patients, and we developed a bioinformatic pipeline at our institution for detecting mutations. RESULTS: We detected causative mutations in 6 of 17 (35%) families. In particular, 11 (65%) families had syndromic diagnosis and 6 (35%) had no syndromic diagnosis before NGS testing. The number of positive diagnoses was 5 of 11 (45%) in the syndromic group and were 1 of 6 (17%) among patients of the no syndromic diagnosis group. CONCLUSION: Diagnostic yields in the present study were higher than in previous reports of genetic and chromosomal tests and WES. The present comprehensive gene-targeted panel test is a powerful diagnostic tool for Mendelian disorders.