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Objectives: To evaluate the incidence of laboratory-confirmed pertussis (LCP) among infants hospitalized with acute respiratory infections (ARIs) and meeting the Centers for Disease Control and Prevention (CDC)-recommended clinical case definition. Methods: An investigator-initiated active surveillance for clinically suspected cases (CSCs) of pertussis screened infants aged ≤6 mo hospitalized with ARIs during January 2020-April 2022 at seven centers across India. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect Bordetella pertussis in nasopharyngeal swabs. Infants were classified as having 'LCP' or 'probable pertussis' (PP). Results: Among 1102 screened infants, 400 participants met the CDC-2020 clinical case definition for pertussis. Of these, 34/400 (8.5%) had LCP and 46/400 (11.5%) had PP. The proportion of participants with LCP and PP was similar among infants aged 0-3 and 4-6 mo [LCP: 0-3 mo, 21/248 (~9%); 4-6 mo, 13/152 (~9%); PP: 0-3 mo, 30/248 (~12%); 4-6 mo, 16/152 (~11%)]. Cough illness lasted ≥2 wk in 3/34 (~9%) and 34/46 (~74%) participants with LCP and PP, respectively. Notably, 80% CSCs had neither LCP nor PP, and a respiratory pathogen apart from B. pertussis was detected in ~32%. Ventilation was required in 12 participants with LCP/PP. Conclusions: In this first study from India based on revised CDC guidelines, the incidence of LCP was 8.5%; cough illness was not a predominant feature. Infants below the age appropriate for vaccination are prone to pertussis-related hospital admissions, ICU care, and ventilation. Maternal immunization may be evaluated for neonatal protection, in addition to other strategies, to decrease disease burden in this highly vulnerable group. Clinical Trial Registration Number: CTRI/2019/12/022449. [ABSTRACT FROM AUTHOR]

RAS-MAPK signaling mediates processes critical to normal development including cell proliferation, survival, and differentiation. Germline mutation of RAS-MAPK genes lead to the Noonan-spectrum of syndromes. Here, we present a patient affected by a 6p-interstitial microdeletion with unknown underlying molecular etiology. Examination of 6p-interstitial microdeletion cases reveals shared clinical features consistent with Noonan-spectrum disorders including short stature, facial dysmorphia and cardiovascular abnormalities. We find the RAS-responsive element binding protein-1 (RREB1) is the common deleted gene in multiple 6p-interstitial microdeletion cases. Rreb1 hemizygous mice display orbital hypertelorism and cardiac hypertrophy phenocopying the human syndrome. Rreb1 haploinsufficiency leads to sensitization of MAPK signaling. Rreb1 recruits Sin3a and Kdm1a to control H3K4 methylation at MAPK pathway gene promoters. Haploinsufficiency of SIN3A and mutations in KDM1A cause syndromes similar to RREB1 haploinsufficiency suggesting genetic perturbation of the RREB1-SIN3A-KDM1A complex represents a new category of RASopathy-like syndromes arising through epigenetic reprogramming of MAPK pathway genes. Mutations in RAS-MAPK pathway genes are implicated in Noonan-spectrum, yet up to 20% of cases have unknown cause. Here, the authors identify RREB1 underlying a 6p microdeletion RASopathy-like syndrome and show that RREB1, SIN3A and KDM1A form a transcriptional repressive complex to control methylation of MAPK pathway genes. [ABSTRACT FROM AUTHOR]